Maintenance Therapy

Trial # Trial Type of Therapy Description Principle Investigator
UPCC 05217*
(NCT03140670)
Rucaparib Phosphate in Treating Patients with Advanced Pancreatic Cancer and a Known Deleterious BRCA1/2 or PALB2 Mutation Targeted Therapy A Phase 2, Open Label Study of Racaparib in Patients with Advanced Pancreatic Cancer and a Known Deleterious Germline or Somatic BRCA or PALB2 Mutation Kim Reiss Binder, MD

*This phase II clinical trial is currently enrolling at the Hematology/Oncology Division of the Abramson Cancer Center.

Investigators at the Basser Center for BRCA and the Pancreatic Cancer Research Center at Penn Medicine are conducting a clinical trial to investigate the poly-ADP ribose polymerase (PARP) inhibitor rucaparib as maintenance therapy in select patients with pancreatic cancer.

Pancreatic cancer is identified with short overall survival, in part because the cancer usually presents in its later stages, and in part because treatment options for advanced pancreatic cancer are somewhat limited. Among the populations at risk for pancreatic cancer, the carriers of certain heritable diseases are prominently represented. These include ~10% of individuals with hereditary Breast and Ovarian Cancer Syndrome (HBOC), a condition linked to mutations of the human tumor suppressor genes BRCA1, BRCA2, and PALB2, among others.

In a development that owes much to clinical research in HBOC, [1] investigators at the Basser Center for BRCA and elsewhere have begun to explore novel agents that may hold promise as targeted therapy for BRCA mutation carriers with pancreatic cancer, including the PARP inhibitor (PARPi) rucaparib. PARPi agents prevent endogenous DNA repair, leading to DNA damage that results in cancer cell death. An orally available, small molecule PARPi, rucaparib has been shown to kill tumors in patients with both germline and somatic BRCA mutations, and to benefit pancreatic cancer patients with a germline BRCA mutation.

The Basser Center participated in a recently completed phase two multi-center study, RUCAPANC (NCT02042378), that evaluated the efficacy and safety of rucaparib in patients with pancreatic cancer (PC) and a known deleterious germline or somatic BRCA mutation. In this trial, 50% of patients with only one prior treatment regimen demonstrated partial response or stable disease for ≥12 weeks. One key variable that seemed to predict success was sensitivity of the tumor to platinum chemotherapy, such as oxaliplatin or cisplatin, suggesting that rucaparib might be better used earlier in the treatment course.

At this time, the Basser Center for BRCA, in collaboration with the Pancreatic Cancer Research Center at Penn Medicine, is conducting a clinical trial to evaluate rucaparib as maintenance therapy in patients with advanced pancreatic cancer and a known deleterious germline or somatic BRCA mutation or PALB2 mutation whose disease has remained stable after treatment with platinum chemotherapy.

Rucaparib in Patients With Advanced Pancreatic Cancer and a Known Deleterious Germline or Somatic BRCA or PALB2 Mutation

The Hematology/Oncology Division of the Abramson Cancer Center is currently enrolling patients for this phase II clinical trial (NCT03140670), which will determine whether rucaparib can be used as a maintenance therapy after chemotherapy in pancreatic cancer patients with BRCA1, BRCA2, or PALB2 mutations. The trial specifically investigates whether patients in this setting can safely discontinue their intravenous chemotherapy, and instead keep their cancer in check with a pill. The hope is that this strategy will effectively control the cancer and improve quality of life for patients. PARP inhibitors have been shown to be effective in several BRCA-related cancers including ovarian cancer, breast cancer, prostate cancer and pancreatic cancer, making these drugs an ideal candidate to study in this context.

Eligible patients must have a mutation in BRCA1, BRCA2, or PALB2, inoperable or metastatic pancreatic adenocarcinoma, and must have completed at least four months of platinum-based chemotherapy without their cancer growing during that treatment. Patients will stop intravenous chemotherapy and instead take rucaparib twice per day. The study is estimated to be enrolling patients for the coming one to two years.

The study’s principal investigator is Kim Reiss Binder, MD, Assistant Professor of Medicine in the Division of Hematology-Oncology at the Hospital of the University of Pennsylvania. Dr. Reiss Binder’s research focuses on the development of new treatments for pancreatic cancer and other gastrointestinal malignancies. For information about enrollment in this study, visit the clinical trial website or contact Colleen Redlinger at colleen.redlinger@uphs.upenn.edu or 215-220-9693.

Access

Basser Center for BRCA
Abramson Cancer Center
Perelman Center for Advanced Medicine
West Pavilion, 3rd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Pancreatic Cancer Research Center
Smilow Center for Translational Research
3400 Civic Center Boulevard
Philadelphia, PA 19104

Basser.org

Published on: March 23, 2018

References

1. Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, et al. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA 1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017;23:4095-4106.

About the Basser Center for BRCA

Led by Executive Director Susan Domchek, MD, the Basser Center for BRCA at Penn Medicine’s Abramson Cancer Center is the first comprehensive center for the research, treatment, and prevention of BRCA-related cancers. Devoted to advancing care for people affected by BRCA gene mutations, the Basser Center’s unique model provides funding for collaborative research, education, and outreach programs around the world.

Penn Faculty Team

Angela R. Bradbury, MD

Associate Professor of Medicine at the Hospital of the University of Pennsylvania

Associate Professor of Medical Ethics and Health Policy

Susan M. Domchek, MD

Director, MacDonald Women’s Cancer Risk Evaluation Center

Executive Director, Basser Center for BRCA

Basser Professor in Oncology

Kara N. Maxwell, MD, PHD

Assistant Professor of Medicine

Assistant Professor of Genetics

Kim A. Reiss Binder, MD

Assistant Program Director of the Hematology/Oncology Fellowship Program

Clinical Associate of Medicine

Assistant Professor of Medicine at the Hospital of the University of Pennsylvania

Payal D. Shah, MD

Assistant Professor of Medicine at the Hospital of the University of Pennsylvania

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