First-ever phase 3 advanced anal cancer trial opens for patient enrollment

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

The EA2176 study aims to enroll 205 patients in the US with inoperable advanced (spread to other parts of the body) squamous cell anal cancer. It seeks newly diagnosed patients who have not yet started treatment along with patients whose cancer has returned or gotten worse following surgery or radiation. Patients who have already received chemotherapy for advanced disease or other investigational drugs are not eligible.

Until recently, patients with advanced inoperable anal cancer were treated with chemotherapy that was not based on randomized clinical trials. In June, the Journal of Clinical Oncology published findings from the worldwide InterAAct trial.

The InterAAct trial 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 the addition of immunotherapy to standard chemotherapy will extend progression-free survival."

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

The EA2176 study 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 either chemotherapy plus nivolumab or chemotherapy alone. Bristol Myers Squibb is providing the nivolumab under a Cooperative Research and Development Agreement with the NCI.

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

Nivolumab was approved for medical use in the US in 2014 and is used to treat several cancers. It remains an experimental, investigational treatment in patients with anal cancer. However, in 2017, Dr. Eng and fellow researchers showed in a phase 2 trial funded by the NCI that nivolumab was well tolerated and effective when used on its own in patients with advanced anal cancer that had progressed after at least one prior systemic treatment (The Lancet Oncology).

According to the American Cancer Society (ACS), about 8600 people in the US will be diagnosed with anal cancer this year. Anal cancer is found mainly in older adults, with an average age being in the early 60s. It occurs nearly twice as often in women as men. It is extremely rare in people younger than 35.

Nine out of ten new anal cancer diagnoses in the US are squamous cell type, associated with HPV. HPV is a virus that nearly every person has at some point in their life. Risk factors that may increase the chance that an HPV infection becomes 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 trial is opening to patient enrollment on a rolling basis at clinical sites in the NCI's National Clinical Trials Network (NCTN). Five network groups, including ECOG-ACRIN, make up the NCTN and are participating in this trial.

The following are the NCTN network groups and the physician-researchers who are EA2176 study champions: 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 the EA2176 trial with David H. Henry, MD, serving as the study champion.

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