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Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Nivolumab

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Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive paclitaxel 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.

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.

Site Public Contact

John A. Ellerton

Shahzad Siddique

Gary L. Buchschacher

Tatjana Kolevska

Syma Iqbal

Jun Gong

Jennifer B. Valerin

Gregory A. Masters

Mohamedtaki A. Tejani

Christopher M. Reynolds

Ranjith B. Dissanayake

Boris Naraev

Josh D. Simmons

Cathy Eng

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.

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.

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.

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Defined as the first of progressive disease or death due to any cause. Analyzed using a stratified two-sided overall 0.05 level log-rank test. Will utilize standard Eastern Cooperative Oncology Group -American College of Radiology Imaging Network interim monitoring for efficacy evaluation.

ORR is the ratio of the number of patients with a complete response or partial response, as defined by Response Evaluation Criteria in Solid Tumors version 1.1, to the total number of treated patients.

Evaluated by a stratified log-rank test, and using a two-sided 0.05 level Cochran Mantel-Haenzel.

Analyses of toxicity will be via frequency tabulations and percentages by worst degree of toxicity and comparisons will be done via chi-square or Fisher's exact tests as appropriate.

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for unresectable anal squamous cell carcinoma