The document provides an introduction to clinical trials for cancer drug development. It discusses moving potential new therapies from preclinical testing in animal models through the different phases of clinical trials in humans. Phase I trials determine safety and dosing, phase II screens for anti-tumor activity, and phase III tests for efficacy in larger patient populations through randomized controlled trials. Ethical review and informed consent are required throughout the clinical trial process to protect patient safety and rights.
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What Are the Different Phases of Clinical Trials?Robert Hindes MD
Well versed in clinical trials and research, particularly those targeting the treatment of hepatitis C virus infection, Robert Hindes, MD, cofounded Trek Therapeutics, PBC, where he functions as the chief medical officer. A contributor to The Lancet Infectious Diseases and other medical journals, Robert Hindes, MD, has managed different phases of clinical trials.
In these slides you can get the information of clinical trials which have four phase I,II,III, IV. before clinical trials, Pre-clinical studies should be completed.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
What Are the Different Phases of Clinical Trials?Robert Hindes MD
Well versed in clinical trials and research, particularly those targeting the treatment of hepatitis C virus infection, Robert Hindes, MD, cofounded Trek Therapeutics, PBC, where he functions as the chief medical officer. A contributor to The Lancet Infectious Diseases and other medical journals, Robert Hindes, MD, has managed different phases of clinical trials.
In these slides you can get the information of clinical trials which have four phase I,II,III, IV. before clinical trials, Pre-clinical studies should be completed.
When a new drug/device/surgical procedure/treatment or other potential medical innovation is developed it must be thoroughly tested to ensure that it is safe and does what it is supposed to be.
This presentation will provide a basic overview of clinical research process.
This presentation was made at the PAMM winter meeting in Verona (Italy) February 2019 and intended students to go through the basic methods used for phase I clinical trials.
Presented at PhUSE 2013
The evaluation of efficacy in oncology studies, in particular for solid tumors, is pretty standard and well defined by several regulatory guidance (e.g. EMA and FDA), including some specific cancer type guidance (e.g. NSCLC from FDA).
Although some references will be also given for non-solid tumors, the paper will mainly focus on solid tumors efficacy
endpoints.
Overall Survival, Best Overall Response as per RECIST criteria, Progression Free Survival (PFS), Time to Progression (TTP), Best Overall Response Rate are some of the key efficacy indicators that will be discussed.
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
Medical Students 2010 - Slide 5 - J.B. Vermorken - Introduction to Clincial Trials
1. Introduction to Clinical Trials Jan B. Vermorken, MD, PhD Department of Medical Oncology Antwerp University Hospital Edegem, Belgium ESO student course, Ioannina, 2010
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5. From Lab….. To Clinical Trials…. To Standard Practice Laboratory data Effective Therapy
12. Moving a New Therapy from the Lab to the Clinic Clinical Evaluation Laboratory Experiments River of Unknowns
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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 -
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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
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
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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
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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
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
54. R esponse E valuation C riteria I n S olid T umours RECIST guidelines
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Editor's Notes
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.
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.
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%.
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%.
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.