NCT04444921

EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients

A Randomized Phase III Study of Immune Checkpoint Inhibition With Chemotherapy in Treatment-Naive Metastatic Anal Cancer Patients

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 205 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase 3 trial compares the addition of nivolumab to chemotherapy (carboplatin and paclitaxel) versus usual treatment (chemotherapy alone) for the treatment of anal cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach.

Detailed description

PRIMARY OBJECTIVE: I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved progression-free survival (PFS) versus systemic chemotherapy alone. SECONDARY OBJECTIVES: I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved overall survival (OS) versus systemic chemotherapy alone. II. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved objective response using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 versus systemic chemotherapy alone. III. To evaluate toxicity profiles of the two regimens. IV. To elucidate the role of the human papillomavirus (HPV) circulating cell-free deoxyribonucleic acid (cfDNA) viral load on PFS with the hypothesis that longer PFS will be associated with viral load. OUTLINE: Patients are randomized to 1 of 2 arms. Randomization will be 2:1 favoring the experimental regimen, Arm B. ARM A: Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1 month, then every 3 months for 2 years.

Conditions

• Anal Basaloid Carcinoma
• Anal Canal Cloacogenic Carcinoma
• Metastatic Anal Squamous Cell Carcinoma
• Recurrent Anal Squamous Cell Carcinoma
• Stage III Anal Cancer AJCC v8
• Stage IV Anal Cancer AJCC v8
• Unresectable Anal Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Carboplatin	Given IV
BIOLOGICAL	Nivolumab	Given IV
DRUG	Paclitaxel	Given IV

Timeline

• Start date: 2020-11-17
• Primary completion: 2027-03-31
• Completion: 2027-03-31
• First posted: 2020-06-24
• Last updated: 2026-04-13

Locations

582 sites across 1 country: United States

Regulatory

• FDA-regulated drug study