Improving the Quality of Cancer Clinical Trials Workshop Summary (2008) / Chapter Skim
Currently Skimming:
Reports from the Case Study Discussion Groups
Reports from the Case Study Discussion Groups
Pages 89-100
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From page 89... ...
Herbst presented a summary of his group's breakout session on adaptive trial design. His group agreed on a number of issues, including the variability of adaptive trial designs and the notion that adaptive trials are not a new phenomenon -- for a long time, many investigators have been using a few of these adaptive designs in their clinical trials, most notably sequential monitoring with early stopping boundaries.
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From page 90... ...
Adaptive designs must be prospective, which requires extra work before trials begin. Extra costs and potential delays in setting up adaptive trials may arise due to the need for increased communication with government regulators and local oversight boards, and the potential need for a larger drug supply.
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From page 91... ...
During his summary, Dr. Herbst reiterated this concern about potential bias in response-adaptive randomized trials, but added that "although this needs to be looked at in any trial and analyzed and is a real concern, the belief was that we could go forward despite this." He also expressed concern about the potential bias being introduced by revealing interim trial results to investigators, patients, and the investment community, as Dr.
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From page 92... ...
Dr. Darlene Rosario of Mannkind Corporation added that even many patients participating in placebo-controlled randomized studies do not receive a personal benefit from their participation.
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From page 93... ...
Dr. Doroshow pointed out that when the IRB reviewed his study of PARP inhibition in tumor biopsies, the IRB noted that because of the extensive preclinical work done by the investigators, the data generated by their tumor analyses would be more accurate than data typically garnered from a Phase I study.
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From page 94... ...
Dr. Evelhoch noted that PET FDG measures of tumor metabolism demonstrated a metabolic effect even in the absence of a traditional clinical response, and enabled some of Amgen's drugs to progress further in the clinical trial hierarchy than they would have if only standard radiologic measures of tumor response were used.
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From page 95... ...
The group requested that the FDA establish a pathway for qualifying imaging biomarkers akin to that used to qualify FDG PET -- one that is mechanism-based and not limited to use on a specific organ or a similarly narrowed application. The group also suggested that the validation process for tracers used as research tools be differentiated from that needed for imaging agents used for clinical diagnostic purposes.
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From page 96... ...
mass spectrometry system to detect protein signatures associated with longer survival in 139 advanced lung cancer patients following treatment with tyrosine kinase inhibitors gefitinib or erlotinib. In this retrospective study, he found the elevated production of eight key proteins in blood serum linked to longer survival.
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From page 97... ...
Kris and Pao also developed a transgenic mouse lung cancer model, with the same EGFR mutations that cause lung cancer in humans, to screen for more effective tyrosine kinase inhibitors. "This is a nice example of a mouse model using transgenic technology in order to do preclinical studies," Dr.
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From page 98... ...
The lengthy FDA approval process is not necessarily required for some predictive biomarker tests performed in laboratories, for which only the laboratory is subject to CMS scrutiny under CLIA. The costs of such tests are likely to be reimbursed if there is enough evidence for their usefulness in compendia or other published data, Dr.
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From page 99... ...
Dr. David Chang reported the results of his prospective analysis of more than 400 archival tissues, which indicated that a wild-type KRAS in colon cancers predicted prolonged survival following treatment with an EGFR antibody, whereas patients with tumors that had KRAS mutations did not benefit at all from that therapy.
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From page 100... ...
Massion said. Such standardization and guidelines, as well as incorporating biomarker tests early in the development process, should help to reduce the costs of biomarker development, provide stronger evidence for improved outcomes, and thus make biomarker test reimbursement by third 21See http://cancergenome.nih.gov/about/index.asp.
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