The first Phase 3 advanced anal cancer study opens for patient enrollment

Reviewed by Emily Henderson, B.Sc.November 16, 2020

The first ever randomized Phase 3 clinical trial in patients with advanced anal canal cancer is now open and enrolling patients. Anal cancer is a rare disease. The vast majority (90%) of new cases are of the squamous cell type, associated with a human papillomavirus (HPV) infection. The new study (study EA2176) is for this patient group. It will find out whether adding the drug nivolumab, which uses the immune system to fight cancer, to standard chemotherapy will reduce symptoms and stop the growth of tumors for a few months or more (progression-free survival). The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) designed the new study in collaboration with the International Rare Cancers Initiative (IRCI). The study is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health.

Study EA2176 aims to enroll 205 patients in the United States with inoperable advanced squamous cell carcinoma (spread to other parts of the body). Look for newly diagnosed patients who have not yet started treatment along with patients whose cancer has returned or worsened following surgery or radiotherapy. Patients who have already received chemotherapy for advanced disease or other investigational drugs are not eligible.

Until recently, patients with inoperable advanced anal cancer were treated with chemotherapy that was not based on randomized clinical trials. In June, the Journal of Clinical Oncology results published by the international study InterAAct.

The InterAAct study established the combination of carboplatin and paclitaxel as the standard initial chemotherapy treatment for inoperable anal cancer. Now, we are taking the next step for patients and exploring whether adding immunotherapy to standard chemotherapy will extend progression-free survival. “

Cathy Eng, MD, Lead Investigator, Vanderbilt-Ingram Cancer Center

Study EA2176 is comparing standard chemotherapy with or without nivolumab, an immune therapy. Patients will be randomly assigned by a computer in a 2: 1 fashion to receive chemotherapy plus nivolumab or chemotherapy alone. Bristol Myers Squibb supplies nivolumab under a cooperative research and development agreement with NCI.

“Study EA2176 is an important study because it reflects extensive discussions among members of the International Rare Cancers Initiative,” said co-researcher Al B. Benson, III, MD (Northwestern University, Robert H. Lurie Comprehensive Cancer Center) and vice president of ECOG-ACRIN. “Globally, this study represents the next step in defining the optimal treatment for patients with advanced anal cancer after InterAAct.”

Nivolumab was approved for medical use in the United States in 2014 and is used to treat several cancers. It remains an experimental and experimental treatment in patients with anal cancer. However, in 2017, Dr. Eng and other investigators demonstrated in an NCI-funded phase 2 study that nivolumab was well tolerated and effective when used alone in patients with advanced anal cancer that had progressed after at least one previous systemic treatment.The Lancet Oncology).

According to the American Cancer Society (ACS), approximately 8600 people in the United States will be diagnosed with anal cancer this year. Anal cancer is found mainly in the elderly, with an average age in the early 1960s. It occurs almost twice as often in women than in men. It is extremely rare in people under the age of 35.

Nine out of ten new diagnoses of anal cancer in the United States are of the squamous cell type, associated with HPV. HPV is a virus that almost every person has at some point in their life. Risk factors that can increase the chance of an HPV infection becoming cancerous are immunosuppression, sexual activity, tobacco use, and older age.

Individuals with HIV, a virus that attacks the immune system, are also at risk of developing anal cancer.

In extremely rare cases, people who don’t have these risk factors also develop anal cancer.

The study opens to patient enrollment on an ongoing basis at NCI’s National Clinical Trials Network (NCTN) clinical sites. Five networking groups, including ECOG-ACRIN, make up the NCTN and are participating in this study.

The following are the NCTN network groups and physician-researchers who are champions of the EA2176 study: Alliance for Clinical Trials in Oncology, Rona Yeager, MD; NRG Oncology, Mohamed Salem, MD; and SWOG Cancer Research Network, Van Morris, MD.

The AIDS Malignancy Consortium participates in study EA2176 with David H. Henry, MD serving as the study champion.