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

Plain English Summary

EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying 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. Tests a new treatment combining chemotherapy and immunotherapy for metastatic anal cancer. For patients with inoperable, recurrent, or metastatic anal cancer. Participation involves receiving IV chemotherapy and immunotherapy treatments. Alternative treatments include standard chemotherapy alone. The trial aims to enroll 205 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 18, with confirmed anal squamous cell carcinoma, and inoperable or recurrent disease. Not eligible if pregnant, have active brain metastasis, or have certain cardiac conditions. Must have measurable disease and meet specific blood and organ function criteria. This trial is studying 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, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the time until the cancer progresses, which is crucial for patients' survival. The specific primary outcome measures are: Progression-free survival (PFS) (Up to 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to improve outcomes for metastatic anal cancer patients by testing a new combination therapy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets 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, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high approval probability for this innovative treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have inoperable or recurrent anal cancer and meet the eligibility criteria. Participation involves regular IV treatments and monitoring for side effects. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 205 participants

Interventions

• DRUG: Carboplatin — Given IV
• BIOLOGICAL: Nivolumab — Given IV
• DRUG: Paclitaxel — Given IV

Primary Outcomes

• Progression-free survival (PFS) (Up to 2 years)

Secondary Outcomes

• Objective response rate (ORR) (Up to 2 years)
• Overall survival (Time between treatment randomization and death by any cause, assessed up to 2 years)
• Incidence of adverse events (Up to 2 years)
• Association of PFS with human papillomavirus (HPV) circulating cell-free deoxyribonucleic acid (DNA) viral load (Up to 2 years)

Full Eligibility Criteria

Inclusion Criteria:

* Patient must have inoperable, recurrent, or metastatic disease not amenable to curative therapy
* Patient must have histological or cytological confirmation of anal squamous cell carcinoma (includes basaloid and cloacogenic lesions) from the primary tumor or a newly diagnosed recurrent/metastatic lesion
* Patient must be \>= 18 years of age
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 0-1
* Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and based on radiologic assessment performed \< 4 weeks prior to randomization
* Patient receiving palliative (limited-field) radiation therapy is allowed, as long as the lesion treated for palliation is not a target lesion and is \> 7 days from completion from palliative radiation
* Patients with brain metastasis are eligible if patient is asymptomatic and if treatment ended \> 3 months prior to randomization. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression within 4 weeks prior to randomization
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study with a minimum sensitivity of 25 IU/L or equivalent units of Bacille Calmette-Guerin (BCG), within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Patients of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception or to abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment
* Absolute neutrophil count \>= 1,500/mcL (obtained \< 14 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained \< 14 days prior to randomization)
* Hemoglobin (Hgb) \>= 9 g/dL for males and \>= 9 g/dL for females (obtained \< 14 days prior to randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained \< 14 days prior to randomization)
* Aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) /alanine transferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN (obtained \< 14 days prior to randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) (obtained \< 14 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (ART) with CD4 count \>= 200 or have a CD4 count \< 200 but an undetectable viral load are eligible

  * All HIV+ patients should be under the care of an infectious diseases specialist. If a relationship with an infectious diseases specialist is not established, an infectious disease specialist should be consulted. Records of all viral counts and peripheral T-cell counts should be documented in order to follow these values over the course of treatment
  * All patients must be willing to undergo testing for HIV testing if not tested within the past 12 months
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy (if indicated)
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Patients with a history of congestive heart failure (CHF) or who are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must be willing to undergo evaluation of cardiac function including electrocardiogram (EKG) and echocardiogram (ECHO) as clinically indicated
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or c

Trial Locations

• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Kingman Regional Medical Center, Kingman, Arizona, United States
• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma, Metastatic Anal Squamous Cell Carcinoma, Recurrent Anal Squamous Cell Carcinoma, Stage III and IV Anal Cancer, Unresectable Anal Squamous Cell Carcinoma

More Anal Basaloid Carcinoma Trials

View all Anal Basaloid Carcinoma clinical trials