DF/HCC Experimental Therapeutics Clinical Trials Network
The Dana-Farber/Harvard Cancer Center (DF/HCC) is one of twelve Lead Academic Organizations (LAOs) selected to be part of the National Cancer Institute (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN). DF/HCC investigators utilize their experience and expertise in clinical drug development to contribute to the ETCTN’s innovative early phase cancer clinical trials.
The DF/HCC LAO is comprised of the Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Massachusetts General Hospital, and the Beth Israel Deaconess Medical Center.
The focus of the ETCTN is on research and development of new cancer treatments with particular emphasis on tumor characterization, biomarker development, and understanding cancer biology. DF/HCC researchers collaborate with the NCI and other ETCTN institutions by providing expertise in areas such as cancer biology, biomarker assay development, imaging and molecular characterizations. DF/HCC investigators take part in the design of drug development plans for agents in the National Cancer Institute (NCI) portfolio and physician-investigators have the opportunity to serve as the national protocol chair for ETCTN trials or support other ETCTN investigators by becoming participating investigators on studies led by other ETCTN institutions.
Involvement with the ETCTN provides excellent opportunities for physicians who wish to pursue a career in clinical research. DF/HCC has a strong history of supporting junior investigators and within the ETCTN priority is placed on career development and the mentored training of junior investigators.
- Conduct early phase clinical trials of NCI Cancer Therapy Evaluation Program (CTEP)-sponsored agents in high priority areas of unmet medical needs.
- Efficiently activate and conduct ETCTN clinical trials in compliance with timelines established by the Operational Efficiency Working Group (OEWG).
- Utilize DF/HCC expertise to understand and assess the molecular target(s) of the agents being studied and develop appropriate biomarker assays to select patients whose tumors are most likely to respond to the agents.
- Promote collaboration among institutions and investigators by working with the NCI and other ETCTN sites to achieve the objectives of the NCI in establishing an integrated network for conducting molecularly-driven early phase cancer treatment trials.
- Integrate molecular characterization, pharmacology, cancer biology, and imaging into clinical trials.
NCI-CTEP-sponsored trials have always comprised a significant component of the tri-institutional Harvard Phase 1 Program, led by Drs. Donald Kufe and Bruce Chabner. The first grant under a U01 mechanism to support these trials was awarded in 1993, with Dr. Kufe as the Harvard Principal Investigator. Three subsequent renewals carried the U01 through 2013, with a mandate to support NCI-CTEP-sponsored Phase 1 studies. At DFCI, MGH and BIDMC, this grant also supported a limited number of Phase 2 studies.
Under the U01 grant, DF/HCC led and contributed substantially to trials of agents targeting signal transduction, angiogenesis, cell cycle, epigenetic targets, anti-apoptotic proteins and immune checkpoints. Below is a sampling of studies conducted under the U01:
- Signal Transduction: Cetuximb/Pertuzumab in colorectal cancer; ARQ197 (cMETi) in triple negative breast cancer; Vemurfanib/Cabozantinib in Melanoma; MK2206 (AKTi) in endometrial, ovarian and HER2+ breast cancer; Selumetinib (MEKi) in BRAF mutant tumors.
- Angiogenesis: Bevacizumab pharmacodynamic study; Bevacizumab + chemoradiation in rectal cancer; cediranib monotherapy in high-grade serous ovarian cancer, glioblastoma, hepatocellular cancer, head and neck cancer; Biomarker study of sorafenib in soft tissue sarcoma
- Cell Cycle: Flavopiridol trials pre-dated current agents and allowed development of pharmacodynamics markers that were used for currently approved agents; CDK2 inhibition in melanoma; trials of KSP (mitotic kinase) inhibitors
- Epigenetics: Early work on HDACs with p21Waf1/Cip1 as a biomarker
- Anti-apoptotic proteins: Early work on obataclax in CLL
- Immuno-Oncology: Trials demonstrating the utility of combining GVAX and ipilimumab in melanoma
In 2013, CTEP announced plans to establish the Experimental Therapeutics Clinical Trials Network (ETCTN) and launched a national competition for ETCTN membership. DF/HCC competed via a UM1 mechanism to become a Lead Academic Organization (LAO) within the ETCTN, and was one of 12 LAOs chosen for the conduct of NCI-CTEP early phase trials (primarily Phase 1).
Since the original 2013 award, DF/HCC has received UM1 supplements facilitating (1) expansion of the portfolio to Phase 2 trials; (2) funding of genomic analyses (targeted NextGen sequencing, whole-exome sequencing and RNA-seq) performed at the BWH Center for Advanced Molecular Diagnostics and the DFCI/Broad Institute Center for Cancer Precision Medicine; (3) collection of blood samples to be used for CTC isolation and generation of patient-derived xenograft models; and (4) development of biomarkers for DNA repair and immuno-oncology studies, as well as liquid biopsies from patients harboring EGFR mutant NSCLC.
DF/HCC has led and participated in multiple Drug Development Project Teams and routinely leads 15-20 active trials within the ETCTN, while participating in an additional 25-30 trials led by other ETCTN sites.
The NCI has established collaborative agreements with pharmaceutical companies which allow ETCTN clinical trial investigators access to drug(s). A list of CTEP agreements and agents can be found here.