Immunotherapy combo shows promise for tough anal cancer

NCT ID NCT02314169

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jul 31, 2026 · Updated 1 time

Summary

This study tests two immunotherapy drugs, nivolumab and ipilimumab, in people with anal cancer that has spread and not responded to prior treatment. The goal is to see if these drugs can shrink tumors or slow cancer growth. About 143 adults with advanced squamous cell carcinoma of the anal canal are taking part.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

143 people

The number who actually took part.

Started

May 2015

Expected to finish

Mar 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Patients must have histologically or cytologically confirmed previously treated metastatic squamous cell carcinoma of the anal canal * Patients must have measurable disease according to the standard Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CT scans or MRIs used to assess the measurable disease must have been completed within 28 days prior to study drug initiation * Patients must have been treated with at least one prior systemic treatment for incurable advanced or metastatic SCCA of the anal canal; prior treatment for metastatic disease is not required for patients who develop new metastatic lesions during or within 6 months of completion of chemoradiation for limited-stage disease; patients who receive chemotherapy for incurable advanced or metastatic SCCA of the anal canal must wait a minimum \>= 28 days (6 weeks for nitrosoureas or mitomycin C) after the date of completion of chemotherapy prior to initiating treatment with nivolumab on this study; patients who undergo palliative radiotherapy to a site of tumor must wait a minimum \>= 28 days from the date of completion of radiotherapy prior to initiating treatment with nivolumab (Part A and B) or nivolumab +/- Ipilimumab (Part B) on this study * Patients must be of age \>= 18 years at the time of study registration; because no dosing or adverse event data are currently available on the use of nivolumab in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky \>= 80%) * Leukocytes \>= 2,000/mcL * Absolute neutrophil count \>= 1,500/mcL * Hemoglobin \>= 9.0 gm/dL * Platelets \>= 100,000/mcL * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN * Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) * Before study enrollment, women of child bearing potential must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy; the subject must sign an informed consent form documenting this discussion; the effects of nivolumab and ipilimumab on the developing human fetus are unknown; for this reason women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; women of childbearing potential MUST have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab with or without ipilimumab; the minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG; if the pregnancy test is positive, the subject must not receive nivolumab with or without ipilimumab and must not be enrolled in the study * Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes * WOCBP receiving nivolumab (Parts A+B) or nivolumab and ipilimumab (Part B) will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product; men receiving nivolumab (Parts A+B) or nivolumab and ipilimumab (Part B only) and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product; these durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days * Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately; if, following initiation of the investigational product, it is subsequently discovered that a study subject is pregnant or may have been pregnant at the time of investigational product exposure, including during at least 6 half-lives after product administration, the investigational product will be permanently discontinued in an appropriate manner (e.g., dose tapering if necessary for subject safety); the investigator must immediately notify BMS of this event and record the pregnancy on the Pregnancy Surveillance Form (not an severe adverse event \[SAE\] form); initial information on a pregnancy must be reported immediately to BMS, and the outcome information provided once the outcome is known; completed Pregnancy Surveillance Forms must be forwarded to BMS according to SAE reporting procedures; any pregnancy that occurs in a female partner of a male study participant should be reported to the sponsor. Information on this pregnancy will be collected on the Pregnancy Surveillance Form; protocol-required procedures for study discontinuation and follow-up must be performed on the subject unless contraindicated by pregnancy (e.g., X-ray studies); other appropriate pregnancy follow-up procedures should be considered if indicated; in addition, the investigator must report and follow-up on information regarding the course of the pregnancy, including perinatal and neonatal outcome; infants should be followed for a minimum of 8 weeks * Ability to understand and the willingness to sign a written informed consent document * Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and have been stable for at least three months prior to registration; eligible subjects should be neurologically asymptomatic; there is no magnetic resonance imaging (MRI) evidence of progression for a minimum of 4 weeks after treatment is complete and within 28 days prior to the first dose of nivolumab administration; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration * Willingness for evaluation of cardiac function including electrocardiography (EKG) and echocardiogram (ECHO) cardiogram for any patients with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs as clinically indicated * All patients must be willing to undergo testing for human immunodeficiency virus (HIV) testing if not tested within the past 6 months * If HIV+ positive, all patients infected with human immunodeficiency virus (HIV) may be eligible for study provided that their CD4+ count \>= 300/uL; their viral load is undetectable; they are currently receiving highly active antiretroviral therapy (HAART) * All HIV+ patients will be under the care of an infectious diseases specialist; if a relationship with an infectious diseases specialist is not established, infectious disease specialist will be consulted; records of all viral counts and peripheral T-cell counts must be sent to the study coordinator in order to follow these values over the course of treatment * All patients must be willing to be tested for hepatitis screening; patients co-infected with hepatitis B virus and/or hepatitis C virus may be included in this study provided that their liver function tests remain within the limits listed above; patients must be followed by a hepatologist during the course of this study Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier (i.e., grade \>= 2 AE present); palliative (limited-field) radiation therapy is permitted, as long as the lesion being considered for palliative radiation is not a target lesion * Patients who are receiving any other investigational agents * Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-programmed cell death ligand 2 (PD-L2), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways * History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab (Parts A+ B) and/or ipilimumab (Part B) * History of severe hypersensitivity reaction to any monoclonal antibody * 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 * Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease * Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =\< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =\< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years

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Conditions

The condition(s) this trial relates to.

anal canal cancer anal canal carcinoma anal canal squamous cell carcinoma anus neoplasm cloacogenic carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Anal canal squamous cell carcinoma Metastatic anal canal carcinoma Stage IV anal cancer ajcc V8

Contacts and locations

Locations

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States
Duke University Medical Center

Durham, North Carolina, 27710, United States
Los Angeles General Medical Center

Los Angeles, California, 90033, United States
MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States
Nebraska Medicine-Bellevue

Bellevue, Nebraska, 68123, United States
Nebraska Medicine-Village Pointe

Omaha, Nebraska, 68118, United States
Northwestern University

Chicago, Illinois, 60611, United States
Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States
Parkland Memorial Hospital

Dallas, Texas, 75235, United States
Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States
Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States
Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States
Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States
Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States
Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, 06385, United States
Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States
Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418, United States
Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, 06708, United States
Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States
UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States
UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States
UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States
USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States
UT MD Anderson Cancer Center

Houston, Texas, 77030, United States
UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States
UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, 76104, United States
University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada
University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States
University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States
University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462, United States
University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116, United States
University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States
University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States
University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States
University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States
University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States
University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States
VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States
Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States
Washington University School of Medicine

St Louis, Missouri, 63110, United States
Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States
Yale University

New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

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