The FINANCIAL — The Alliance Foundation Trials, LLC (AFT), the Austrian Breast & Colorectal Cancer Study Group (ABCSG) and Pfizer Inc. on August 26 announced the launch of the Palbociclib Collaborative AdjuvantStudy, or PALLAS.
This global Phase 3 clinical trial for patients with early-stage breast cancer is being conducted in conjunction with Breast International Group (BIG), German Breast Group (GBG), National Surgical Adjuvant Breast and Bowel Project (NSABP) and PrECOG, LLC (PrECOG). The PALLAS trial will evaluate whether the addition of IBRANCE (palbociclib), developed by Pfizer, to standard therapy will improve disease-free survival and prevent the disease from recurring. Patients treated in this study will have cancers that are hormone receptor-positive (HR+), meaning their growth is fueled by the hormone estrogen, but are negative for human epidermal growth factor receptor 2 (HER2-), a different tumor-associated protein. About 60 to 65 percent of breast cancers in the United States fall into this category, according to Pfizer.
“We are delighted that Alliance was chosen to co-lead the PALLAS trial along with our partners at ABCSG,” said Monica M. Bertagnolli, MD, president and chief executive officer of AFT, and group chair and principal investigator of the Alliance for Clinical Trials in Oncology. “This exciting study examines a new CDK 4/6 inhibitor that has already demonstrated an impact for breast cancer patients with metastatic disease. The goal is to determine whether IBRANCE can also improve the disease-free survival rate in patients with surgically resectable disease.”
“After intensively working together among trial leadership on the scientific conception, operational preparation and seamless transatlantic cooperation for this clinical trial, we are excited that this study, with the potential to revolutionize adjuvant therapy for the most common type of breast cancer, is now ready to start,” said Professor Michael Gnant, MD, FACS, president of the ABCSG, and head of the Breast Health Center Vienna. “We are convinced that this global venture has potential to bring great benefit to our breast cancer patients.”
A hallmark of cancer cell growth is loss of control of the cell cycle, leading to unregulated growth and spread of cancer. A promising strategy to overcome this process involves inhibition of enzymes called cyclin-dependent kinases (CDKs), which allows re-establishment of control of cell growth. iii,iv Recent research has shown that two related enzymes – CDK 4 and CDK 6 – are among the primary proteins that accelerate cancer cell growth, and may be particularly important in HR+ breast tumors. iii,iv Research also indicates that combining CDK 4/6 inhibitors with endocrine therapy is beneficial in patients with advanced breast cancer.iii,iv The new oral, anti-cancer drug IBRANCE blocks CDK 4/6.ii
IBRANCE was approved in February 2015 by the U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal women with estrogen receptor-positive (ER+)/HER2- advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival, the length of time during or after treatment a patient lives with a disease but does not get worse.ii Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.
“We have seen exciting news about IBRANCE in 2015, not only from the accelerated approval based on PALOMA-1, but also from the results of the PALOMA-3 study, a Phase 3 trial showing the addition of IBRANCE to the hormone medicine fulvestrant in pre-treated patients with metastatic HR+/HER2- breast cancer improved clinical outcomes,” said Erica L. Mayer, MD, MPH, co-principal investigator of the trial for AFT, Assistant Professor of Medicine at the Harvard Medical School and Senior Physician at the Susan F. Smith Center for Women’s Cancers and at the Dana-Farber Cancer Institute.
“The primary endpoint of the PALLAS trial is to look at the time to disease recurrence in patients who have stage 2 or stage 3 breast cancer,” Dr. Mayer said. “The study is also enriched with an expansive correlative science program that includes analyses of patient tissue and blood samples, as well as an in depth analysis of patient adherence to oral medication and patients’ quality of life while on study.”
The PALLAS trial is a prospective, two-arm, international, multicenter, randomized, open-label Phase 3 study. The trial is open to premenopausal and postmenopausal women or men with stage 2 or stage 3 HR+/HER2- early breast cancer. Participants will be randomized (selected by chance) to one of two treatment arms. One study arm will treat patients with IBRANCE (at a dose of 125 mg orally once daily, day 1 to day 21 followed by seven days off treatment in a 28-day cycle) for two years and standard endocrine adjuvant therapy for at least five years. The other study arm will treat patients with standard endocrine adjuvant therapy alone for at least five years. Participants will be recruited worldwide. Approximately 4,600 people are expected to enroll in the trial.
“We’re looking for ways that we can prevent recurrence of breast cancer in every patient. IBRANCE appears to be very promising in that regard because it boosted the effect of anti-estrogen treatments in women who already have recurrent, metastatic breast cancer,” said Angela DeMichele, MD, MSCE, co-principal investigator for PrECOG, Miller Associate Professor of Breast Cancer Excellence in the Rowan Breast Center and Associate Professor of Medicine and Epidemiology at the Abramson Cancer Center of the University of Pennsylvania.
The scope of the PALLAS trial is global. AFT and the ABCSG have brought together a collaborative group of breast cancer specialists from around the world to team up with Pfizer to form a unique public-private cancer research partnership aimed at bringing more innovative therapies to patients in more efficient ways.
“Collaborations of this kind are crucial to advance the science and general understanding of how we can best treat breast cancer,” said Maria Koehler, MD, PhD, vice president of Strategy, Innovation and Collaborations for Pfizer Oncology. “Working together, we will be able to efficiently answer important clinical questions in order to potentially bring IBRANCE to patients with early-stage breast cancer who need the treatment most.”
“Pfizer is honored to partner with prominent breast cancer research groups to explore the use of IBRANCE for women and men with HR+/HER2- early-stage breast cancer, which affects millions of patients each year globally. This collaboration allows Pfizer to tap into many of the most respected scientific minds and well-established large global research networks to conduct a large, international Phase 3 trial,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.
Currently, the new study is open to physicians and medical facilities throughout the U.S. if they are associated with Alliance, NSABP or PrECOG. The study will be available to non-U.S. sites beginning in October through an extended academic core network, including the ABCSG and BIG.