Facilitating Collaborations to Develop Combination Investigational Cancer Therapies Workshop Summary (2012) / Chapter Skim
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Appendix A: Examples of Collaborations
Appendix A: Examples of Collaborations
Pages 77-90
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From page 77... ...
Some of these assays detect more than one molecular mechanism simultaneously, including an assay that has antibodies that detect all the different phosphorylation sites on MET. NCI is also funding researchers to develop multiplex assays appropriate for use in the clinic with a single biopsy.
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From page 78... ...
Information about this resource and how to obtain it can be found on the Division of Cancer Treatment and Diagnosis Developmental Therapeutics Program website.1 Preclinical Models for Combinations To assess the effects of combining anticancer agents on tumor growth inhibition, NCI's toxicogenomics program is testing 5,000 unique combi nations for the 100 commercially available anticancer drugs across many clinically relevant concentrations on the NCI-60 panel, which includes 60 human tumor cell lines. For about 10 percent of the combinations, some synergistic effects appear to be greater than the additive effects alone.
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From page 79... ...
Doroshow said, the Department of Health and Human Services' Office of General Counsel prohibited NCI from purchasing or synthesizing patented agents for research purposes. But that policy changed in 2009, and NCI has acquired more than 300 investigational agents anticancer potential for in vitro testing, including multiple representatives of each class.
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From page 80... ...
Usually multiple drugs and biomarkers require multiple trials, each with its own IND. Even when a drug is successful in the first phase of testing, the trial has to be stopped and a new one created to continue testing in the next phase.
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From page 81... ...
Fundraising is separated from the contribution of the agents." An independent agent selection committee consisting of oncologists without conflict of interests chooses which agents are tested in the trial, based on rigorous scientific criteria. 4 caBIG stands for the cancer Biomedical Informatics Grid, an information network that enables members of the cancer community to share data and knowledge.
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From page 82... ...
Following biomarker analysis of their tumor sample under an umbrella protocol, patients were adaptively randomized to one of four treatments with targeted cancer therapies, including one treatment which was a combination of two agents, and one treatment that was a multitargeted inhibitor. Because of the involvement of different research groups and pharmaceutical companies, each treatment had its own separate Phase II clinical trial.
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From page 83... ...
The protocol includes a mandatory biopsy, initial adaptive randomization, statistical modeling and biomarker selection, and a refined randomization phase where the best predictive markers are selected. Two of the four treatment arms include combination therapies.
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NOTE: AZ = AstraZeneca, FDA = Food and Drug Administration, IGFR1 = insulinlike growth factor receptor 1, IND = investigational new drug, IRB = institutional review board, IP = intellectual property, MDACC = MD Anderson Cancer Center, OSI = OSI Pharmaceuticals, PI = principal investigator, POC = proof of concept, RPTD = recommended phase treatment dose. SOURCE: Papadimitrakopoulou presentation (June 14, 2011)
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From page 85... ...
Patients enrolled in PI3K clinical trials are asked to provide a tumor biopsy sample at entry as well as a subsequent biopsy if the cancer pro gresses. These biopsies are analyzed for the same resistance mutations seen in the mouse models, and are used to guide which experimental therapy patients receive.
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From page 86... ...
. To expedite the contract and budget negotiations required between industry and publicly funded investigators before the launch of a collaborative trial, the Consortium and NCI reviewed copies of 78 redacted clinical trial agreements and identified 45 key concepts related to intellectual property, study data, subject injury, indemnification, confidentiality, and publication rights.
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It plans to work with NCI as a safe harbor for this effort because NCI currently has a robust biomarker program, according to Dr. Gregory Curt, chair of the Life Sciences Consortium and the U.S.
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, the Biotechnology Industry Organization, and the Pharmaceutical Research and Manufacturers of America. The Biomarkers Consortium was prompted by the growing awareness of the importance of validated biomarkers in the success of targeted therapies.
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There are 27 member sites involved in CITN, including all the large cancer centers, and the first clinical trials are expected to be launched by the end of 2011, according to Dr.
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The Foundation collaborates or contracts with stakeholders, such as FDA, university consortia, public– private partnerships, academia, nonprofits, and industry, to efficiently and effectively advance its goals and priorities. The Foundation is currently working on regulatory issues related to developing multiple drug regimens for tuberculosis as well as identifying common mechanisms of cardiotoxicity for oncology drugs.9 9 See http://www.focr.org/component/option,com_eventlist/Itemid,41/id,27/view, details/ (accessed December 14, 2001)
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