Newswise — Academic and Community Cancer Research United (ACCRU) today announced the opening of a two-arm, randomized phase III, FDA registration trial of eribulin compared to standard weekly paclitaxel as first- or second-line chemotherapy for individuals with human epidermal growth factor receptor 2 (HER2) negative, locally recurrent, unresectable or metastatic breast cancer. The study (ACCRU trial RU011201I) aims to enroll approximately 910 patients. Patient recruitment is underway in ACCRU member sites throughout the country. Individuals are randomized in a 1:1 ratio between the experimental and control arms within strata defined by prior taxane exposure, hormone receptor status and line of therapy (1st/2nd). The study was developed by Minetta Liu, M.D., an ACCRU principal investigator and medical oncologist at Mayo Clinic. Sponsorship is provided by Eisai, Inc.
According to Dr. Liu, “Eribulin is one of the few single agent chemotherapeutics associated with an overall survival benefit in patients with heavily pretreated metastatic breast cancer. It is also favorable from the perspective of patient quality of life with its short (2-5 minute) infusion time, the absence of required steroid premedications and general tolerability. This trial will therefore assess the potential benefits of eribulin administration earlier in the course of therapy.”
The opening of the trial is a landmark for ACCRU, a network of more than 85 academic and community cancer centers throughout the United States and Canada. “This trial is somewhat unique because it is investigator-initiated, industry-sponsored, and being conducted solely within the ACCRU network. This is a true collaboration between a pharmaceutical company and academic and community cancer centers with the primary goal of conducting clinical research to improve patient care,” Dr. Liu says.
“The opening of this trial showcases ACCRU’s network capabilities to conduct a large, multicenter trial that includes well-designed translational research that will provide important information for all physicians selecting treatments for patients with metastatic breast cancer,” says Axel Grothey, M.D., ACCRU group chair and oncologist at Mayo Clinic.
Metastatic breast cancer is generally incurable, with few patients achieving long-term survival with standard systemic therapy. Despite a marked increase in the choice of active agents for the treatment of metastatic disease, overall survival has improved incrementally during the last half century. Paclitaxel is a taxane derivative and is among the most active agents in the treatment of breast cancer.
Eribulin is a novel, non-taxane, tubulin-targeted agent which was approved by the Food and Drug Administration in November 2010 for the treatment of metastatic breast cancer in patients with prior exposure to an anthracycline and taxane in either the adjuvant or metastatic setting and who received at least two chemotherapeutic regimens for the treatment of metastatic disease. This study focuses on the administration of eribulin earlier in the treatment of advanced breast cancer.
Correlative studies
The trial includes several embedded translational research substudies, which are designed to answer additional questions about the safety, tolerability and efficacy of eribulin compared to standard paclitaxel therapy.
“These studies will generate additional information that may allow physicians to individualize therapy and maximize benefit from eribulin, paclitaxel, or both,” says Dr. Liu. “We have incorporated innovative tools to assess quality of life through patient self-reporting, and novel laboratory based studies to develop biomarkers for treatment-related benefit as well as toxicity.”
The objectives of the trial’s correlative studies include:
• To evaluate the clinical value and feasibility of collecting patient-reportedsymptom toxicity information via the Patient-Report Outcomes Version of theCommon Terminology Criteria for Adverse Events (PRO-CTCAE); to furthervalidate the PRO-CTCAE sensory neuropathy items; and to compare patient reported neurotoxicity between arms using the EORTC QLQ-CIPN20instrument. (Research coordinated by Ethan Basch, M.D., University of North Carolina.)• To validate polymorphisms in FGD4, EPHA5, and FZD3 as predictors ofperipheral neuropathy from treatment with a microtubule dynamics inhibitor (i.e., eribulin or paclitaxel). (Research coordinated by Deanna Kroetz, Ph.D., University of California, San Francisco.)• To evaluate circulating nucleosomes and the apoptosis associated M30 neoepitope as potential biomarkers associated with clinical benefit from treatment with eribulin specifically or the microtubule dynamics inhibitors in general. (Research coordinated by Minetta Liu, M.D., Mayo Clinic.)• To evaluate circulating cytokines and angiogenic factors as potential biomarkersassociated with clinical benefit from treatment with eribulin specifically or themicrotubule dynamics inhibitors in general. (Research coordinated by Eisai, Inc.)• To evaluate tubulin isotype expression, mutations, and signaling pathwaymodifications in tumor tissue as potential biomarkers associated with clinicalbenefit from treatment with eribulin specifically or the microtubule dynamicsinhibitors in general. (Research coordinated by Eisai, Inc.)
For more information
For more information about the trial, visit http://www.clinicaltrials.gov/ct2/show/NCT02037529?term=RU011201I&rank=1. Treatment sites interested in learning about the trial can contact the ACCRU Research Coordinating Center by email at [email protected] or by phone at 507-538-7448.
About ACCRU
The Academic and Community Cancer Research United (ACCRU) is a clinical research group network of more than 85 academic and community-based cancer treatment clinics and hospitals in the United States and Canada. ACCRU operations are based at the Mayo Clinic Cancer Center in Rochester, Minnesota. This research network was established in 2004 to conduct clinical trials to improve cancer care.
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