A Manual for Participants in Clinical Trials of Investigational Agents ...

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Integrated biomarkers are not used to determine treatment in the trial, but are clearly identified as part of the trial from the beginning and are intended to identify or validate tests planned for use in future trials. Integrated tests are performed on all subjects, and the study includes complete plans for specimen or image collection, laboratory measurements and statistical analysis. The investigator(s) responsible for biomarker measurements must be identified. Even if laboratory test results are not used to determine treatment, if the results will be reported to the patient or his/her physician at any time, then the test must be performed in a CLIA-certified laboratory; additional state or local regulations may apply. As for integral biomarkers, information about the test should be included in the protocol’s Objective(s), Background and Rationale and Statistical Considerations sections, and in other sections as appropriate (e.g., Special Studies or an Appendix). It is essential that the protocol document itself include clear and complete instructions for the acquisition, processing and shipment of specimens and/or imaging data; if specimen collection is mentioned in more than one section of the protocol (for example, in both Procedures for Patient Entry on Study and in an Appendix), be careful to maintain consistency in the instructions. Correlative or ancillary laboratory or imaging studies may be retrospective or exploratory. To enhance opportunities for high-quality retrospective studies, which can be exceptionally informative, investigators are encouraged to build plans for specimen collection and tissue banking into clinical trials. Correlative studies of tests that do not meet the criteria above for either integral or integrated biomarkers may be embedded in the protocol. See Guidelines for Correlative Studies in Clinical Trials (http://ctep.cancer.gov/protocolDevelopment/default.htm#ancillary_correlatives) for information that should be included in the protocol for embedded correlative studies. Section 3 - Investigator’s Manual 2009 10
4 Phase 1 Trials The Development of a Clinical Trial The following three sections explain the policies for phase 1, 2 and 3 clinical investigations with CTEP study agents. For each phase, we outline the scientific objectives for CTEP-supported clinical trials. We also describe which physicians are eligible to study and administer study agents. These two aspects of agent use—study and administration—are formally separate issues. In general, eligibility to study CTEP study agents has been restricted to institutions and investigators approved by peer review; these individuals may include grantees, contractors, Cooperative Group members, physicians affiliated with approved cancer centers, and recipients of investigator-initiated clinical research project grants (RO1, PO1). The application of this general rule to each phase of agent development is explained in detail. Except in certain explicitly defined circumstances outlined in the following sections, the administration of study agents is restricted to these investigators. Information regarding the use of investigational agents in phase 0 studies is found in Appendix II. For investigational agents involving a pharmaceutical collaborator and a DCTDsponsored IND, the Investigational Drug Steering Committee (IDSC) is consulted to develop a strategic clinical development plan. The IDSC membership includes principal investigators from NCI phase1 U01 and phase 2 N01 contracts, as well as representatives from Cooperative Groups. Its members include experts in biostatistics, imaging, radiation oncology, and clinical and preclinical pharmacology. The IDSC subgroups assist CTEP with early phase trial prioritization, and address critical scientific issues for the trials (http://ctep.cancer.gov/SpotlightOn/Investigational_Drug_Steering_Committee.htm). 4.1 Scientific Policies of CTEP 4.1.1 Planning of Phase 1 Trials CTEP plans the phase 1 development of each agent prospectively, basing schedule selection and starting doses for phase I clinical trials on experimental data. Generally, each schedule is examined in not more than two studies. From the results of the phase 1 and clinical pharmacology studies, CTEP and its collaborators (investigators, pharmaceutical collaborators and IDSC) decide which schedule to bring forward into phase 2. If the need exists, they may comparatively examine a second schedule later in selected tumors to better define the therapeutic index. 4.1.2 Objectives Phase 1 trials determine a safe and/or biologically effective dose for phase 2 trials and help define adverse effects on normal tissues. In addition, these trials examine the agent's pharmacology which may reveal evidence of antitumor activity. Anticancer agents are not tested in patients unless preclinical activity studies have demonstrated evidence of significant activity in laboratory animals or an appropriate in vitro model. Section 4 - Investigator’s Manual 2009 11
Page 1 and 2: A Manual for Clinical Investigators
Page 3 and 4: 7.1.3 Purpose .....................
Page 5 and 6: 13.4 Responsibilities of Clinical S
Page 7 and 8: 1 Introduction This manual explains
Page 9 and 10: drugs and biologics rests with the
Page 11 and 12: costs might include additional labo
Page 13 and 14: 3 The Clinical Trial Site and the I
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Page 21 and 22: for organ dysfunction studies. The
Page 23 and 24: efore writing a formal LOI. IDB sta
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Page 27 and 28: 5.1.4 Randomized Phase 2 Studies A
Page 29 and 30: • Physician members of CCOPs for
Page 31 and 32: 6 Phase 3 Trials 6.1 Scientific Pol
Page 33 and 34: completed by the Cooperative Group
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Page 43 and 44: • How dose modifications will be
Page 45 and 46: consent forms. However, the informe
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Page 51 and 52: 9 Ordering Investigational Agents f
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14.3 Administration of Investigatio
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• Agents are stored in various pl
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16 Monitoring and Quality Assurance
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16.5 Components of the Quality Assu
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Also, please note that medical reco
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• Even if the agent has been repo
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Appendix I NCI-Cooperative Group-In
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Phase 0 trials do not replace phase
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phase 2 trials enroll 20-30 patient
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the study should be ordered under t
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Appendix IV Key Contact Information
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Appendix V Informed Consent Checkli
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2. Describe risks as outlined in th
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CLINICAL SITE: An institution, coop
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RAB: Regulatory Affairs Branch, htt
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• Agent preparations must be perf
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Procedure for Acute Exposure or Spi
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Appendix VIII National Cancer Insti
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7) Investigational Drug Accountabil
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• Write treatment instructions cl
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• For agent admixtures that can b
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A Manual for Participants in Clinical Trials of Investigational Agents ...

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