A Randomized Phase III Study of Nivolumab After Combined Modality Therapy (CMT) in High Risk Anal Cancer

Plain English Summary

Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma, Anal Margin Squamous Cell Carcinoma, Stage IIB Anal Cancer AJCC v8, Stage III Anal Cancer AJCC v8. Tests how well nivolumab works after combined modality therapy in treating high risk stage II-IIIB anal cancer. For patients who have had previous treatment and are at high risk of cancer returning. Participation involves regular check-ups, scans, and blood tests. Biopsies and colonoscopies may also be required. Alternative treatments include standard chemotherapy and radiation therapy. The trial aims to enroll 344 participants.

Official Summary

This phase III trial investigates how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Age 18 and older. Histologically proven stage IIB, IIIA, IIIB, or IIIC invasive squamous cell carcinoma of the anus or anorectum. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. No active infections or other serious health conditions. This trial is studying Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma, Anal Margin Squamous Cell Carcinoma, Stage IIB Anal Cancer AJCC v8, Stage III Anal Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the time until the cancer returns, which is crucial for patients to understand their prognosis. The specific primary outcome measures are: Disease free survival (Up to 5 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 patients with high risk anal cancer by investigating the effectiveness of nivolumab. 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, Anal Margin Squamous Cell Carcinoma, Stage IIB Anal Cancer AJCC v8, Stage III Anal Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high probability of approval, making this a promising investment opportunity. 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 about the risks and benefits of participating in this trial. Be prepared for regular medical check-ups, scans, and blood tests. 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: 344 participants

Interventions

• PROCEDURE: Biopsy Procedure — Undergo biopsy
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Colonoscopy — Undergo colonoscopy
• PROCEDURE: Computed Tomography — Undergo CT scan
• PROCEDURE: Digital Rectal Examination — Undergo digital rectal examination

Primary Outcomes

• Disease free survival (Up to 5 years)

Secondary Outcomes

• Objective response rate (Up to 5 years)
• Severe toxicity interval (The time between randomization and the occurrence of late severe side effects (up to 5 years))
• Colostomy-free survival (Up to 5 years)
• Overall survival (Up to 5 years)
• Incidence of toxicities (Up to 5 years)

Full Eligibility Criteria

Inclusion Criteria:

* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Age \>= 18 years
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients must have histologically proven stage IIB (T3N0M0 only), IIIA (T2N1M0), IIIB (T4N0M0), or IIIC (T3N1M0, T4N1M0) invasive squamous cell carcinoma of the anus or anorectum, according to the American Joint Committee on Cancer (AJCC) 8th edition; this may include tumors of non-keratinizing histology such as basaloid, transitional cell, or cloacogenic histology; individuals with squamous cell carcinoma of the anal margin are eligible if there is evidence of extension of the primary tumor into the anal canal
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients must have hemoglobin levels of \> 9 g/dL (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patient must have a platelet count of \> 100,000/mm\^3 (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patient's absolute neutrophil count (ANC) level must be \> 1500/mm\^3 (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Serum creatinine must be =\< 1.5 X upper limit of normal (ULN) (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Total bilirubin must be \< 2 X ULN (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Albumin \>= 3.0 g/dL (within 2 weeks prior to registration)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients known to be human immunodeficiency virus (HIV)+ are permitted; patients with CD4 \> 200 and serum HIV viral load of \< 200 copies/mm\^3 are eligible, and in addition:

  * Participants must be purified protein derivative (PPD) negative; alternatively, the QuantiFERON-tuberculosis (TB) Gold In-Tube (QFT-GIT) assay (Cellestis Limited, Carnegie, Australia) can be used; an individual is considered positive for M. tuberculosis infection if the IFN-gamma response to TB antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control); the result must be obtained within 20 weeks prior to enrollment; PPD positive (or Quantiferon assay positive) participants are permitted if prophylaxis has been completed prior to enrollment
  * No history of acquired immune deficiency syndrome (AIDS)-related complications within past year other than a history of low CD4+ T-cell count \> 200/mm\^3 prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to chemoradiotherapy and should not be used as an exclusion criterion if low
  * Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the anal cancer
  * Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 12 weeks following enrollment
  * Patient must have =\< grade 2 diarrhea (participants with grade 1 diarrhea are eligible provided stool for ova/parasites and stool cryptosporidium studies are negative;
  * NOTE: HIV testing is not required for eligibility
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: For patients registering prior to start of chemoradiotherapy, baseline scans must have been completed within 4 weeks prior to registration
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Women of child bearing potential and sexually active males must use accepted and effective method(s) of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 5 months after the last dose of nivolumab (for female patients) and for at least 7 months after the last dose of nivolumab (for male patients)
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Any surgery must have been completed \>= 4 weeks prior to starting study treatment
* REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: No uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* REGISTRATION TO STEP 1 ELIGIBILITY

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• 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
• Fairbanks Memorial Hospital, Fairbanks, Alaska, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Anal Basaloid Carcinoma
• Anal Canal Cloacogenic Carcinoma
• Anal Margin Squamous Cell Carcinoma
• Stage IIB Anal Cancer AJCC v8
• Stage III Anal Cancer AJCC v8
• Anal Cancer
• Squamous Cell Carcinoma
• Cancer
• Immunotherapy
• Immunotherapy for Cancer

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