SlideShare une entreprise Scribd logo
1  sur  50
Introduction to Clinical Trials Jan B. Vermorken, MD, PhD Department of Medical Oncology Antwerp University Hospital Edegem, Belgium  ESO student course, Ioannina, 2011
Outline ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cancer Treatment Today ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Long Term Survival (%) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
From Lab….. To Clinical Trials…. To Standard Practice Laboratory data Effective Therapy
Drug Development ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Anticancer Drug Discovery ,[object Object],[object Object],[object Object],[object Object]
Screening/Compound Based Discovery ,[object Object],[object Object],[object Object]
Preclinical Requirements ,[object Object],[object Object],[object Object],[object Object],[object Object]
Preclinical Evaluation of Cytotoxic Agents ,[object Object],[object Object],[object Object],[object Object],[object Object],IN VITRO IN VIVO Mechanism of action Stage I Stage II
Human Tumor in Nude Mouse
Moving a New Therapy from  the Lab to the Clinic Clinical Evaluation Laboratory Experiments River of Unknowns
Clinical Trials ,[object Object],[object Object],[object Object]
Phase I Design: Selection of Starting Dose ,[object Object],[object Object],[object Object]
Phase I Trials ,[object Object],[object Object],Dose escalating by modified Fibonacci 3 pts 3 pts 3 pts 3 pts 3 pts 3 pts Dose Severe toxicity Recommended dose
Modified Fibonacci Escalation Dose Level Theory Example starting Dose x 1 level 2 2 x level 1 2 level 3 1.67 x level 2 3.3 level 4 1.5 x level 3 5 level 5 1.4 x level 4 6.7 level 6 1.33 x level 5 8.8 level 7 1.33 x level n-1 -
Phase II Trials ,[object Object],[object Object],[object Object],[object Object]
Complete Response: WHO Adapted from World Health Organization, 1980. Primary Tumor Nodes Metastases Disappearance of all clinical, radiologic and biologic signs of tumor Treatment
Partial Response: WHO Treatment Decrease of the multiple of two tumor diameters by at least 50% Adapted from World Health Organization, 1980.
Progression: WHO Increase of the multiple of two tumor diameters by at least 25% Adapted from World Health Organization, 1980. Treatment
Example Calculation PD calculated from lowest sum on study
R esponse  E valuation  C riteria  i n  S olid  T umors (RECIST)   Therasse et al JNCI 2000 ,[object Object],[object Object],[object Object],[object Object],[object Object],* Required confirmation
RECIST Guidelines: Response Criteria ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Example Calculation PD calculated from lowest sum on study
Unidimensional vs. WHO Criteria:  Response Rates  in 4,613 Patients from 14 Studies/Data Sets
New  R esponse  E valuation  C riteria in  S olid  T umours: Revised RECIST Guidelines (verion 1.1) E.A. Eisenhauer, et al. European Journal of Cancer 2009; 45: 228-247
What  HAS NOT  changed in RECIST 1.1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
For example: Response classification same… Time point Response: Patients with Target (+/- non-target) Disease: Target lesions Non-Target lesions New Lesions Overall response CR CR No CR CR Non-CR/Non-PD No PR CR Not evaluated No PR PR Non-PD  or  not all evaluated No PR SD Non-PD  or  not all evaluated No SD Not all evaluated Non-PD No NE PD Any Any PD Any PD Any PD Any Any Yes PD
Summary: What  HAS  changed in RECIST 1.1 RECIST 1.0 RECIST 1.1 Measuring tumor burden 10 targets 5 per organ For response: 5 targets (2 per organ) Lymph node Measure long axis as for other lesions.  Silent on normal size Measure short axis.  Define normal size. Progression definition 20% increase in sum 20% increase and at least  5 mm absolute increase Non-measurable disease PD “ must be unequivocal” Expanded definition to convey impact on overall burden of disease. Examples. Confirmation required Required when  response  primary endpoint—but not PFS New lesions -- New section which includes comment on FDG PET interpretation
New Lesions (1) ,[object Object],[object Object],[object Object],[object Object]
New Lesions (2) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
What is Efficacy? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Phase III Trials Once a new agent has shown activity in phase II, comparative trials are usually designed.  New agent can be given alone or in combination ,[object Object],[object Object],[object Object]
Phase III Trials:  Definitive Tests of Efficacy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
How Much Improvement in Efficacy? ,[object Object],[object Object],[object Object],[object Object],[object Object]
Survival Advantage at 3 years Required by Patients vs Staff to Accept Toxic Treatment % Survival Advantage Threshold Number of subjects From Brundage et al, 1997
Acceptance Thresholds:  By 50% or More of Staff
Acceptance Thresholds:  By 50% or More of Patients
Studies with non-Cytotoxics
“ Non-Cytotoxics” ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Moving a New Therapy from  the Lab to the Clinic Differences between cytotoxic and non-cytotoxic agents Clinical Evaluation Laboratory Experiments River of Unknowns
Preclinical Data: Cytotoxic Agent Dose Effect -- anti-tumor toxicity --
Antitumor Effect: Tumor Regression Time tumor Size control increasing doses new agent
The Bridge to the Clinic for Traditional Cytotoxics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Preclinical Data: Non- Cytotoxic
Antitumor Effect: Growth Delay
The Bridge to the Clinic For Novel Non-Cytotoxics ,[object Object],[object Object],[object Object],[object Object],[object Object]
Ethical Committee: Roles and Function ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Summary ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 

Contenu connexe

Tendances

Glossary Of Clinical Trials Terms
Glossary Of Clinical Trials TermsGlossary Of Clinical Trials Terms
Glossary Of Clinical Trials Terms
Mersedeh Arvaneh
 
Clinical trails
Clinical trailsClinical trails
Clinical trails
Gaurav Kr
 

Tendances (20)

Glossary Of Clinical Trials Terms
Glossary Of Clinical Trials TermsGlossary Of Clinical Trials Terms
Glossary Of Clinical Trials Terms
 
FDA 2013 Clinical Investigator Training Course: The Design of Clinical Trials
FDA 2013 Clinical Investigator Training Course: The Design of Clinical Trials FDA 2013 Clinical Investigator Training Course: The Design of Clinical Trials
FDA 2013 Clinical Investigator Training Course: The Design of Clinical Trials
 
Understanding Clinical Trials
Understanding Clinical TrialsUnderstanding Clinical Trials
Understanding Clinical Trials
 
Clinical trial designs
Clinical trial designsClinical trial designs
Clinical trial designs
 
Clinical trials/ dental implant courses
Clinical trials/ dental implant coursesClinical trials/ dental implant courses
Clinical trials/ dental implant courses
 
Clinical trial design
Clinical trial designClinical trial design
Clinical trial design
 
trial and protocol design
trial and protocol design trial and protocol design
trial and protocol design
 
Clinical research basic things
Clinical research basic thingsClinical research basic things
Clinical research basic things
 
Introduction to Clinical trial
Introduction to Clinical trial Introduction to Clinical trial
Introduction to Clinical trial
 
Importance of clinical trials
Importance of clinical trialsImportance of clinical trials
Importance of clinical trials
 
Features of clinical trials
Features of clinical trialsFeatures of clinical trials
Features of clinical trials
 
Clinical trial design, Trial Size, and Study Population
Clinical trial design, Trial Size, and Study Population Clinical trial design, Trial Size, and Study Population
Clinical trial design, Trial Size, and Study Population
 
Clinical trial
Clinical trialClinical trial
Clinical trial
 
Introduction to clinical research
Introduction to clinical researchIntroduction to clinical research
Introduction to clinical research
 
Clinical trails
Clinical trailsClinical trails
Clinical trails
 
3.clinical trials
3.clinical trials3.clinical trials
3.clinical trials
 
Clinical Trials 101
Clinical Trials 101Clinical Trials 101
Clinical Trials 101
 
Designs of clinical trials
Designs of clinical trialsDesigns of clinical trials
Designs of clinical trials
 
Clinical Research, A Basic Understanding...........
Clinical Research, A Basic Understanding...........Clinical Research, A Basic Understanding...........
Clinical Research, A Basic Understanding...........
 
# 5th lect clinical trial process
# 5th lect clinical trial process# 5th lect clinical trial process
# 5th lect clinical trial process
 

En vedette

Clinical Trials Introduction
Clinical Trials IntroductionClinical Trials Introduction
Clinical Trials Introduction
biinoida
 
Worldwide comprehensive study of guideline on clinical trial
Worldwide comprehensive study of guideline on clinical trialWorldwide comprehensive study of guideline on clinical trial
Worldwide comprehensive study of guideline on clinical trial
RGPV BHOPAL
 
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...
Best Practices
 
Medical device clinical evaluation
Medical device clinical evaluationMedical device clinical evaluation
Medical device clinical evaluation
Malesh M
 

En vedette (20)

Clinical Trials Glossary
Clinical Trials GlossaryClinical Trials Glossary
Clinical Trials Glossary
 
Clinical Trials Introduction
Clinical Trials IntroductionClinical Trials Introduction
Clinical Trials Introduction
 
Clinical Trial Phases
Clinical Trial PhasesClinical Trial Phases
Clinical Trial Phases
 
Clinical Trials - An Introduction
Clinical Trials - An IntroductionClinical Trials - An Introduction
Clinical Trials - An Introduction
 
Worldwide comprehensive study of guideline on clinical trial
Worldwide comprehensive study of guideline on clinical trialWorldwide comprehensive study of guideline on clinical trial
Worldwide comprehensive study of guideline on clinical trial
 
China: Medical Device Regulations
China: Medical Device RegulationsChina: Medical Device Regulations
China: Medical Device Regulations
 
Examples From Medical Device Clinical Trials To Illustrate Advantages Of The ...
Examples From Medical Device Clinical Trials To Illustrate Advantages Of The ...Examples From Medical Device Clinical Trials To Illustrate Advantages Of The ...
Examples From Medical Device Clinical Trials To Illustrate Advantages Of The ...
 
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...
Clinical Affairs Excellence: Benchmarking Clinical Trial Strategies To Ensure...
 
FDA: Designs for Medical Device Clinical Studies
FDA: Designs for Medical Device Clinical Studies FDA: Designs for Medical Device Clinical Studies
FDA: Designs for Medical Device Clinical Studies
 
Understanding how the eu clinical trials directive could have a feedback impa...
Understanding how the eu clinical trials directive could have a feedback impa...Understanding how the eu clinical trials directive could have a feedback impa...
Understanding how the eu clinical trials directive could have a feedback impa...
 
Medical device registration and clinical trial in china (www.cirs md.com)
Medical device registration and clinical trial in china (www.cirs md.com)Medical device registration and clinical trial in china (www.cirs md.com)
Medical device registration and clinical trial in china (www.cirs md.com)
 
INVESTIGATION OF IN-VITRO ANTHELMINTIC AND CYTOTOXIC ACTIVITIES OF ARTABOTRYS...
INVESTIGATION OF IN-VITRO ANTHELMINTIC AND CYTOTOXIC ACTIVITIES OF ARTABOTRYS...INVESTIGATION OF IN-VITRO ANTHELMINTIC AND CYTOTOXIC ACTIVITIES OF ARTABOTRYS...
INVESTIGATION OF IN-VITRO ANTHELMINTIC AND CYTOTOXIC ACTIVITIES OF ARTABOTRYS...
 
Clinical trial on Medical Device: complete development
Clinical trial on Medical Device: complete developmentClinical trial on Medical Device: complete development
Clinical trial on Medical Device: complete development
 
Recist
RecistRecist
Recist
 
Medical device clinical evaluation
Medical device clinical evaluationMedical device clinical evaluation
Medical device clinical evaluation
 
Driving Performance Excellence in the Regulatory Affairs Function at Medical ...
Driving Performance Excellence in the Regulatory Affairs Function at Medical ...Driving Performance Excellence in the Regulatory Affairs Function at Medical ...
Driving Performance Excellence in the Regulatory Affairs Function at Medical ...
 
2
22
2
 
Globalization of Clinical Trials: Mutual acceptance of Medical Device data
Globalization of Clinical Trials: Mutual acceptance of Medical Device dataGlobalization of Clinical Trials: Mutual acceptance of Medical Device data
Globalization of Clinical Trials: Mutual acceptance of Medical Device data
 
The basics of clinical trials
The basics of clinical trialsThe basics of clinical trials
The basics of clinical trials
 
Full recist violet
Full recist violetFull recist violet
Full recist violet
 

Similaire à Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - Introduction to Clinical Trials

NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...
NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...
NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...
European School of Oncology
 
Radiation oncology
Radiation oncologyRadiation oncology
Radiation oncology
Rad Tech
 
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Mina Max
 
Potential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentPotential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug development
Bhaswat Chakraborty
 
Melanoma Nancy Shum And Anne Marcy Intro To Clinical Data Management
Melanoma   Nancy Shum And Anne Marcy Intro To Clinical Data ManagementMelanoma   Nancy Shum And Anne Marcy Intro To Clinical Data Management
Melanoma Nancy Shum And Anne Marcy Intro To Clinical Data Management
cunniffe6
 
Drug risk assessment 23 4-2010
Drug risk assessment 23 4-2010Drug risk assessment 23 4-2010
Drug risk assessment 23 4-2010
RobHeerdink
 
Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...
Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...
Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...
European School of Oncology
 
Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...
Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...
Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...
CanCertainty
 

Similaire à Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - Introduction to Clinical Trials (20)

NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...
NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...
NY Prostate Cancer Conference - T. Rancati - Session 7: Predicting radio-indu...
 
Clinical trials and evidence
Clinical trials and evidenceClinical trials and evidence
Clinical trials and evidence
 
Radiation oncology
Radiation oncologyRadiation oncology
Radiation oncology
 
UAB Pulmonary board review study design and statistical principles
UAB Pulmonary board review study  design and statistical principles UAB Pulmonary board review study  design and statistical principles
UAB Pulmonary board review study design and statistical principles
 
2014-10-22 EUGM | WEI | Moving Beyond the Comfort Zone in Practicing Translat...
2014-10-22 EUGM | WEI | Moving Beyond the Comfort Zone in Practicing Translat...2014-10-22 EUGM | WEI | Moving Beyond the Comfort Zone in Practicing Translat...
2014-10-22 EUGM | WEI | Moving Beyond the Comfort Zone in Practicing Translat...
 
The use of deauville criteria in follow up assessment of response to therapy ...
The use of deauville criteria in follow up assessment of response to therapy ...The use of deauville criteria in follow up assessment of response to therapy ...
The use of deauville criteria in follow up assessment of response to therapy ...
 
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
 
Potential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentPotential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug development
 
Melanoma Nancy Shum And Anne Marcy Intro To Clinical Data Management
Melanoma   Nancy Shum And Anne Marcy Intro To Clinical Data ManagementMelanoma   Nancy Shum And Anne Marcy Intro To Clinical Data Management
Melanoma Nancy Shum And Anne Marcy Intro To Clinical Data Management
 
Drug risk assessment 23 4-2010
Drug risk assessment 23 4-2010Drug risk assessment 23 4-2010
Drug risk assessment 23 4-2010
 
Clinical trial design
Clinical trial designClinical trial design
Clinical trial design
 
Phase I trials - Educational course at the PAMM-2019 winter meeting
Phase I trials - Educational course at the PAMM-2019 winter meetingPhase I trials - Educational course at the PAMM-2019 winter meeting
Phase I trials - Educational course at the PAMM-2019 winter meeting
 
Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...
Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...
Rare Solid Cancers: An Introduction - Slide 3 - P. Bruzzi - Methodological as...
 
Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...
Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...
Surrogate Endpoints: Are drug review processes flexible enough to expedite pa...
 
Efficacy endpoints in Oncology
Efficacy endpoints in OncologyEfficacy endpoints in Oncology
Efficacy endpoints in Oncology
 
Neoadjuvant Therapy of Rectal Cancer: Pathologic Versus Clinical CR
Neoadjuvant Therapy of Rectal Cancer: Pathologic Versus Clinical CRNeoadjuvant Therapy of Rectal Cancer: Pathologic Versus Clinical CR
Neoadjuvant Therapy of Rectal Cancer: Pathologic Versus Clinical CR
 
radford2015.pdf
radford2015.pdfradford2015.pdf
radford2015.pdf
 
Sample size in clinical research 2021 april
Sample size in clinical research 2021 aprilSample size in clinical research 2021 april
Sample size in clinical research 2021 april
 
Radiation Therapy as a Drug and Use in Metastatic Disease
Radiation Therapy as a Drug and Use in Metastatic DiseaseRadiation Therapy as a Drug and Use in Metastatic Disease
Radiation Therapy as a Drug and Use in Metastatic Disease
 
Clinical Proof of Concept (PoC)
Clinical Proof of Concept (PoC)Clinical Proof of Concept (PoC)
Clinical Proof of Concept (PoC)
 

Plus de European School of Oncology

ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
European School of Oncology
 
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
European School of Oncology
 
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
European School of Oncology
 
A. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomasA. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomas
European School of Oncology
 
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomasA. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
European School of Oncology
 
S. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccineS. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccine
European School of Oncology
 
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
European School of Oncology
 
J.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the artJ.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the art
European School of Oncology
 
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
European School of Oncology
 
T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer
European School of Oncology
 
N. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancerN. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancer
European School of Oncology
 
S. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the artS. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the art
European School of Oncology
 
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
European School of Oncology
 
G. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the artG. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the art
European School of Oncology
 
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
European School of Oncology
 

Plus de European School of Oncology (20)

ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
 
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
 
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
 
W. Hassen - Bladder cancer - Guidelines
W. Hassen - Bladder cancer - GuidelinesW. Hassen - Bladder cancer - Guidelines
W. Hassen - Bladder cancer - Guidelines
 
A. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomasA. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomas
 
H. Khaled - Bladder cancer - State of the art
H. Khaled - Bladder cancer - State of the artH. Khaled - Bladder cancer - State of the art
H. Khaled - Bladder cancer - State of the art
 
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomasA. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
 
1 azim
1 azim1 azim
1 azim
 
H. Azim - Lymphomas - State of the art
H. Azim - Lymphomas - State of the artH. Azim - Lymphomas - State of the art
H. Azim - Lymphomas - State of the art
 
S. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccineS. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccine
 
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
 
J.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the artJ.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the art
 
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
 
V. Kesic - Cervical cancer - State of the art
V. Kesic - Cervical cancer - State of the art V. Kesic - Cervical cancer - State of the art
V. Kesic - Cervical cancer - State of the art
 
T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer
 
N. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancerN. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancer
 
S. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the artS. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the art
 
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
 
G. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the artG. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the art
 
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
 

Dernier

Mckinsey foundation level Handbook for Viewing
Mckinsey foundation level Handbook for ViewingMckinsey foundation level Handbook for Viewing
Mckinsey foundation level Handbook for Viewing
Nauman Safdar
 
!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...
!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...
!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...
DUBAI (+971)581248768 BUY ABORTION PILLS IN ABU dhabi...Qatar
 
Jual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan Cytotec
Jual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan CytotecJual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan Cytotec
Jual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan Cytotec
ZurliaSoop
 

Dernier (20)

Rice Manufacturers in India | Shree Krishna Exports
Rice Manufacturers in India | Shree Krishna ExportsRice Manufacturers in India | Shree Krishna Exports
Rice Manufacturers in India | Shree Krishna Exports
 
Falcon Invoice Discounting: Tailored Financial Wings
Falcon Invoice Discounting: Tailored Financial WingsFalcon Invoice Discounting: Tailored Financial Wings
Falcon Invoice Discounting: Tailored Financial Wings
 
Falcon's Invoice Discounting: Your Path to Prosperity
Falcon's Invoice Discounting: Your Path to ProsperityFalcon's Invoice Discounting: Your Path to Prosperity
Falcon's Invoice Discounting: Your Path to Prosperity
 
SEO Case Study: How I Increased SEO Traffic & Ranking by 50-60% in 6 Months
SEO Case Study: How I Increased SEO Traffic & Ranking by 50-60%  in 6 MonthsSEO Case Study: How I Increased SEO Traffic & Ranking by 50-60%  in 6 Months
SEO Case Study: How I Increased SEO Traffic & Ranking by 50-60% in 6 Months
 
Pre Engineered Building Manufacturers Hyderabad.pptx
Pre Engineered  Building Manufacturers Hyderabad.pptxPre Engineered  Building Manufacturers Hyderabad.pptx
Pre Engineered Building Manufacturers Hyderabad.pptx
 
TVB_The Vietnam Believer Newsletter_May 6th, 2024_ENVol. 006.pdf
TVB_The Vietnam Believer Newsletter_May 6th, 2024_ENVol. 006.pdfTVB_The Vietnam Believer Newsletter_May 6th, 2024_ENVol. 006.pdf
TVB_The Vietnam Believer Newsletter_May 6th, 2024_ENVol. 006.pdf
 
How to Get Started in Social Media for Art League City
How to Get Started in Social Media for Art League CityHow to Get Started in Social Media for Art League City
How to Get Started in Social Media for Art League City
 
Katrina Personal Brand Project and portfolio 1
Katrina Personal Brand Project and portfolio 1Katrina Personal Brand Project and portfolio 1
Katrina Personal Brand Project and portfolio 1
 
Buy Verified TransferWise Accounts From Seosmmearth
Buy Verified TransferWise Accounts From SeosmmearthBuy Verified TransferWise Accounts From Seosmmearth
Buy Verified TransferWise Accounts From Seosmmearth
 
CROSS CULTURAL NEGOTIATION BY PANMISEM NS
CROSS CULTURAL NEGOTIATION BY PANMISEM NSCROSS CULTURAL NEGOTIATION BY PANMISEM NS
CROSS CULTURAL NEGOTIATION BY PANMISEM NS
 
Falcon Invoice Discounting: Unlock Your Business Potential
Falcon Invoice Discounting: Unlock Your Business PotentialFalcon Invoice Discounting: Unlock Your Business Potential
Falcon Invoice Discounting: Unlock Your Business Potential
 
Falcon Invoice Discounting: Aviate Your Cash Flow Challenges
Falcon Invoice Discounting: Aviate Your Cash Flow ChallengesFalcon Invoice Discounting: Aviate Your Cash Flow Challenges
Falcon Invoice Discounting: Aviate Your Cash Flow Challenges
 
Mckinsey foundation level Handbook for Viewing
Mckinsey foundation level Handbook for ViewingMckinsey foundation level Handbook for Viewing
Mckinsey foundation level Handbook for Viewing
 
Uneak White's Personal Brand Exploration Presentation
Uneak White's Personal Brand Exploration PresentationUneak White's Personal Brand Exploration Presentation
Uneak White's Personal Brand Exploration Presentation
 
Cannabis Legalization World Map: 2024 Updated
Cannabis Legalization World Map: 2024 UpdatedCannabis Legalization World Map: 2024 Updated
Cannabis Legalization World Map: 2024 Updated
 
BeMetals Investor Presentation_May 3, 2024.pdf
BeMetals Investor Presentation_May 3, 2024.pdfBeMetals Investor Presentation_May 3, 2024.pdf
BeMetals Investor Presentation_May 3, 2024.pdf
 
Getting Real with AI - Columbus DAW - May 2024 - Nick Woo from AlignAI
Getting Real with AI - Columbus DAW - May 2024 - Nick Woo from AlignAIGetting Real with AI - Columbus DAW - May 2024 - Nick Woo from AlignAI
Getting Real with AI - Columbus DAW - May 2024 - Nick Woo from AlignAI
 
!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...
!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...
!~+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUD...
 
Jual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan Cytotec
Jual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan CytotecJual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan Cytotec
Jual Obat Aborsi ( Asli No.1 ) 085657271886 Obat Penggugur Kandungan Cytotec
 
Phases of Negotiation .pptx
 Phases of Negotiation .pptx Phases of Negotiation .pptx
Phases of Negotiation .pptx
 

Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - Introduction to Clinical Trials

  • 1. Introduction to Clinical Trials Jan B. Vermorken, MD, PhD Department of Medical Oncology Antwerp University Hospital Edegem, Belgium ESO student course, Ioannina, 2011
  • 2.
  • 3.
  • 4.
  • 5. From Lab….. To Clinical Trials…. To Standard Practice Laboratory data Effective Therapy
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11. Human Tumor in Nude Mouse
  • 12. Moving a New Therapy from the Lab to the Clinic Clinical Evaluation Laboratory Experiments River of Unknowns
  • 13.
  • 14.
  • 15.
  • 16. Modified Fibonacci Escalation Dose Level Theory Example starting Dose x 1 level 2 2 x level 1 2 level 3 1.67 x level 2 3.3 level 4 1.5 x level 3 5 level 5 1.4 x level 4 6.7 level 6 1.33 x level 5 8.8 level 7 1.33 x level n-1 -
  • 17.
  • 18. Complete Response: WHO Adapted from World Health Organization, 1980. Primary Tumor Nodes Metastases Disappearance of all clinical, radiologic and biologic signs of tumor Treatment
  • 19. Partial Response: WHO Treatment Decrease of the multiple of two tumor diameters by at least 50% Adapted from World Health Organization, 1980.
  • 20. Progression: WHO Increase of the multiple of two tumor diameters by at least 25% Adapted from World Health Organization, 1980. Treatment
  • 21. Example Calculation PD calculated from lowest sum on study
  • 22.
  • 23.
  • 24. Example Calculation PD calculated from lowest sum on study
  • 25. Unidimensional vs. WHO Criteria: Response Rates in 4,613 Patients from 14 Studies/Data Sets
  • 26. New R esponse E valuation C riteria in S olid T umours: Revised RECIST Guidelines (verion 1.1) E.A. Eisenhauer, et al. European Journal of Cancer 2009; 45: 228-247
  • 27.
  • 28. For example: Response classification same… Time point Response: Patients with Target (+/- non-target) Disease: Target lesions Non-Target lesions New Lesions Overall response CR CR No CR CR Non-CR/Non-PD No PR CR Not evaluated No PR PR Non-PD or not all evaluated No PR SD Non-PD or not all evaluated No SD Not all evaluated Non-PD No NE PD Any Any PD Any PD Any PD Any Any Yes PD
  • 29. Summary: What HAS changed in RECIST 1.1 RECIST 1.0 RECIST 1.1 Measuring tumor burden 10 targets 5 per organ For response: 5 targets (2 per organ) Lymph node Measure long axis as for other lesions. Silent on normal size Measure short axis. Define normal size. Progression definition 20% increase in sum 20% increase and at least 5 mm absolute increase Non-measurable disease PD “ must be unequivocal” Expanded definition to convey impact on overall burden of disease. Examples. Confirmation required Required when response primary endpoint—but not PFS New lesions -- New section which includes comment on FDG PET interpretation
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
  • 35.
  • 36. Survival Advantage at 3 years Required by Patients vs Staff to Accept Toxic Treatment % Survival Advantage Threshold Number of subjects From Brundage et al, 1997
  • 37. Acceptance Thresholds: By 50% or More of Staff
  • 38. Acceptance Thresholds: By 50% or More of Patients
  • 40.
  • 41. Moving a New Therapy from the Lab to the Clinic Differences between cytotoxic and non-cytotoxic agents Clinical Evaluation Laboratory Experiments River of Unknowns
  • 42. Preclinical Data: Cytotoxic Agent Dose Effect -- anti-tumor toxicity --
  • 43. Antitumor Effect: Tumor Regression Time tumor Size control increasing doses new agent
  • 44.
  • 47.
  • 48.
  • 49.
  • 50.  

Notes de l'éditeur

  1. 5. Drug Development: Preclinical Evaluation of Cytotoxic Agents Preclinical evaluation of potentially useful cytotoxic agents comprises in vitro and in vivo analyses. In vitro analysis may include assays designed to evaluate the mechanism of action of compounds against specific mechanistic or molecular targets or activity at the cellular level in terms of cytotoxicity, growth inhibition, or differentiation. Thereafter, Stage I in vivo testing is designed to identify the maximum tolerated dose and dose-limiting toxicities of the compound, in addition to preliminary efficacy findings. Stage II in vivo testing is designed to define the spectrum of activity, schedule dependency, optimal route of administration, potential for cross resistance with other agents, and potential usefulness in combination therapies.
  2. 9. Drug Development: Clinical Endpoints: Complete Remission One criterion for evaluating response to chemotherapy involves degrees of remission from the signs of disease. A complete remission is a response to treatment in which all clinical, radiologic, and biologic signs of a tumor have been observed to disappear. All fields demonstrating the primary tumor, node-positive disease, and metastatic disease must be confirmed to be disease-free for designation as a complete remission.
  3. 10. Drug Development: Clinical Endpoints: Partial Remission Remission that is less than complete may be designated as partial remission if the tumor bulk has been reduced by at least 50%.
  4. 11. Drug Development: Clinical Endpoints: Disease Progression A response designation of disease progression indicates failure of therapy to arrest tumor growth. Specifically, tumor growth must exceed the multiple of two tumor diameters by at least 25%.
  5. The ultimate test of any agent is the phase III trial. These are large and seek to address differences in treatments using outcomes such as overall survival, cure rate and quality of life. Issues of bias are minimized by the randomized design. The sample size determines the power with which one can detect differences of interest between treatment arms.