Nivolumab With or Without Ipilimumab in Treating Patients With Refractory Metastatic Anal Canal Cancer
A Multi-Institutional Phase 2 Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Refractory Metastatic Squamous Cell Carcinoma of the Anal Canal
15 other identifiers
interventional
143
2 countries
56
Brief Summary
This phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with anal canal cancer that has not responded to previous treatment (refractory) and that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2015
Longer than P75 for phase_2
56 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 10, 2014
CompletedFirst Posted
Study publicly available on registry
December 11, 2014
CompletedStudy Start
First participant enrolled
May 13, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2025
CompletedResults Posted
Study results publicly available
April 22, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 21, 2027
ExpectedApril 22, 2026
April 1, 2026
9.8 years
December 10, 2014
January 21, 2026
April 1, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Overall Response Rate: Number of Participants With Response (Part A)
Responses assessed using computed tomography (CT) scans or magnetic resonance imaging according to standard Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria in order to assess disease progression. Complete Response (CR): Disappearance all target lesions; any pathological lymph nodes reduction in short axis to \< 10 mm (\< 1 cm). Partial Response (PR): \> 30% decrease in sum diameters of target lesions. Progressive Disease (PD): \> 20% increase in sum diameters lesions. (Note: appearance of one or \> new lesions considered progressions). Stable Disease (SD): Neither shrinkage qualify for PR nor increase for PD.
Up to 2 years
Progression-free Survival (PFS) (Part B)
From initiation of treatment with nivolumab until the time of disease progression, time measured in months. Kaplan-Meier analysis performed to estimate the median progression-free survival with a 90% confidence interval.
Time period from the date of randomization to the date of PD or death whichever occurred first, assessed up to 2 years
Secondary Outcomes (6)
Treatment-related Toxicities That Occurred in at Least 1 Patient (Part A)
Adverse event data were collected during treatment (up to 100 months) and through 100 days post treatment
Overall Survival (Part A)
From initiation of treatment until death, assessed up to 2 years
Overall Survival (Part B)
From initiation of treatment until death, assessed up to 2 years
Progression-free Survival (Part A)
From initiation of treatment with nivolumab until the time of disease progression, assessed up to 2 years
Overall Response Rate (Part B)
Up to 2 years
- +1 more secondary outcomes
Other Outcomes (1)
Expression of Biomarkers Using Immunohistochemistry and Blood Samples (Part A)
Up to time of treatment discontinuation
Study Arms (3)
Part A (nivolumab)
EXPERIMENTALPatients receive nivolumab IV over 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
Part B Arm I (nivolumab)
EXPERIMENTALPatients receive nivolumab IV over 30 minutes once every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
Part B Arm II (nivolumab, ipilimumab)
EXPERIMENTALPatients receive nivolumab as in Arm I. Patients also receive ipilimumab IV over 30 minutes once every 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Undergo CT scan
Given IV
Given IV
Undergo MRI
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (56)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, 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 Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, 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
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123, United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Parkland Memorial Hospital
Dallas, Texas, 75235, 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
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Related Publications (2)
Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL, Xiao L, Bekaii-Saab T, Vence L, Blando J, Mahvash A, Foo WC, Ohaji C, Pasia M, Bland G, Ohinata A, Rogers J, Mehdizadeh A, Banks K, Lanman R, Wolff RA, Streicher H, Allison J, Sharma P, Eng C. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017 Apr;18(4):446-453. doi: 10.1016/S1470-2045(17)30104-3. Epub 2017 Feb 18.
PMID: 28223062RESULTMorris VK, Ciombor KK, Xiao L, Ochieng JK, Marmonti E, Polite B, Weinberg BA, Krauss JC, Hays J, Mukherjee S, Aranha O, Iqbal S, Shields T, Benson AB, Kazmi S, Lieu C, Hochster H, Whisenant J, Haymaker C, Eng C. NCI9673 (Part B): ETCTN Randomized Phase II Study of Nivolumab With or Without Ipilimumab in Refractory, Metastatic Squamous Cell Carcinoma of the Anal Canal. J Clin Oncol. 2026 Feb 20;44(6):497-507. doi: 10.1200/JCO-25-00929. Epub 2026 Jan 7.
PMID: 41499716DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Cathy Eng, MD
- Organization
- Vanderbilt-Ingram Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Cathy Eng
Yale University Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 10, 2014
First Posted
December 11, 2014
Study Start
May 13, 2015
Primary Completion
February 15, 2025
Study Completion (Estimated)
March 21, 2027
Last Updated
April 22, 2026
Results First Posted
April 22, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share