Phase 3 study of three-drug regimen for biliary tract cancer exceeds enrollment goal
Positive results from a phase 2 study of a three-drug regimen to treat biliary tract cancer paved the way for the first randomized phase 3 study of its kind in the U.S., led by Rachna Shroff, MD, MS.
Shroff, a member of Healio’s Women in Oncology Peer Perspective Board, is chief of the section of GI medical oncology, director of the clinical trials office, vice chair of clinical research in the department of medicine and associate professor of medicine in the division of hematology/oncology at University of Arizona Cancer Center.
“My area of research is focused on developing novel therapeutics for pancreatic and biliary cancers,” Shroff told Healio. “These are diseases that have really dismal prognoses and very limited therapeutic options, which is what drew me to the field in the first place. Chemotherapy is the primary treatment for both diseases, so my focus has been in targeted therapies and immunotherapy for pancreatic and biliary cancers while building on the chemotherapy backbones that we have.”
The phase 2 study, performed at MD Anderson Cancer Center and the Mayo Clinic in Arizona, involved 60 patients with advanced biliary tract cancers. Patients received cisplatin and Gemzar (gemcitabine, Eli Lilly and Co.) in combination with Abraxane (nab-paclitaxel, Celgene).
Median PFS was 11.8 months (95% CI, 6-15.6) at median follow-up of 12.2 months (95% CI, 9.4-19.4) with a partial response rate of 45% and disease control rate of 84%. Median OS was 19.2 months (95% CI, 13.2 months to not estimable).
“Based on that phase 2 study, I am the national principal investigator for SWOG 1815, which is the first randomized phase 3 study in biliary cancers in the United States,” Shroff said. “The primary endpoint is overall survival, to see if patients live longer with the three-drug regimen vs. the standard-of-care two-drug regimen.”
Shroff said that when the study was initially designed, the NCI — the study’s sponsor through the National Clinical Trials Network — was worried about accruing enough patients due to the rarity of biliary tract cancers. The planned enrollment was 268 patients.
“This study opened really quickly, with the first patient enrolled in February 2019,” Shroff said. “By February of 2020, we had already almost hit 268 patients. We blew our expected accrual rate out of the water.”
Shroff and colleagues spoke with the NCI and expanded the study from 268 to 441 planned patients, based on the rapid accrual. The study reopened at the end of June and has enrolled 333 patients to date.
“This will be an important study because it will be definitively answering a question and hopefully offering a new chemotherapy treatment for our patients,” Shroff said. “I think the other important thing is that we’ve proven to the NCI, to the country and to pharma, that we can do a big study in a rare disease population for a group of patients who have very limited drug options.”
Shroff said the “future is bright” in the field of GI oncology.
“I started in this field more than 10 years ago, and back then we had one chemotherapy drug for pancreatic cancers. Although it doesn’t seem like we’ve moved the needle forward that much, we have improved survival in that time and we have a much better understanding of the profiles of pancreatic and biliary cancers. With this understanding, we can build smarter drugs.”
Additionally, Shroff highlighted the importance of mentorship, from both men and women.
“We are seeing more and more women in GI oncology and it’s a wide-open playing field,” Shroff said. “It’s important to seek out those mentors who can help you learn how to write and design clinical trials so we can bring drugs to patients, and to have your career development path outlined and paved by senior key opinion leaders.”