NCI ID NCI-2020-04334
NCT ID NCT04444921
CTEP ID EA2176
Primary Purpose TREATMENT
Anatomic Sites Anus
Minimum Age 18 Years
Maximum Age 999 Years
Gender BOTH
Lead Org ECOG-ACRIN Cancer Research Group
Principal Investigator Cathy Eng
NCI Site View on ClinicalTrials.gov

EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients

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.

Eligibility

Inclusion Criterea

  • 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
  • Absolute neutrophil count >= 1,500/mcL (obtained < 14 days prior to randomization)
  • Platelets >= 100,000/mcL (obtained < 14 days prior to randomization)
  • Hemoglobin (Hb) >= 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 caregiver and/or family member available will also be considered eligible
  • Patients must agree to not receive live vaccines while on this study

Exclusion Criterea

  • Women 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 females 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 female of childbearing potential is defined as any woman, regardless of sexual orientation or 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).
  • Women of childbearing potential and sexually active males must not expect to conceive or father 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 for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with women of childbearing potential (WOCBP)
  • Patient must not have had previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable recurrent or metastatic anal cancer (previous use of radiotherapy or chemoradiotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumor lesions are present at randomization for the purpose of tumor response assessment or 2) in the absence of non-irradiated target tumor lesions, progression of the irradiated tumor lesions according to the RECIST criteria version 1.1 is documented)
  • Patient must not have current or recent (within 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study
  • Patient must not have had prior immunotherapy
  • Patient must not have a history of known hypersensitivity reaction to any platinum or taxane-based chemotherapy or monoclonal antibody
  • Patient must not have 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). 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. Patients with any of these are ineligible because of the risk of recurrence or exacerbation of autoimmune disease
  • Patient must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of randomization. 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
  • Patient must not have had major surgery performed =< 28 days prior to randomization
  • Patient must not have a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
  • Patient must not have a serious active infection requiring IV antibiotics at time of randomization
  • Patient must not have other primary malignancy within the last 3 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer, or any other cancer from which the patient has been disease-free for at least 3 years
  • Patient must not have known peripheral neuropathy > grade 1 at the time of randomization (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)

Participating Clinics

OptumCare Cancer Care at MountainView


3150 North Tenaya Way
Suite 510 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Henderson


2904 West Horizon Ridge Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Las Vegas


3006 South Maryland Parkway
Suite 100 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Henderson


52 North Pecos Road
Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Medical Center


6450 Medical Center Street
Las Vegas, NV 89148-2405
Map

702-384-0013
research@sncrf.org

Carson Tahoe Regional Medical Center


1535 Medical Parkway
Pharmacy Suite C Carson City, NV 89703
Map

702-384-0013
research@sncrf.org

PCR Oncology


584 Camino Mercado
Arroyo Grande, CA 93420
Map

702-384-0013
research@sncrf.org

Sunrise Hospital and Medical Center


3186 South Maryland Parkway
Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Renown Regional Medical Center


1155 Mill Street
Reno, NV 89502
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Southeast


3980 South Eastern Avenue
Las Vegas, NV 89119
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Fort Apache


6160 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Vegas Tenaya


2851 North Tenaya Way
Suite 100 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Summerlin


655 North Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Henderson


10001 South Eastern Avenue
Suite 108 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Saint Mary's Regional Medical Center


235 West Sixth Street
Reno, NV 89503
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Town Center


653 North Town Center Drive
Suite 402 Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Southeast Henderson


1505 Wigwam Parkway
Suite 130 Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Central


624 South Tonopah Drive
Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Northwest


7445 Peak Drive
Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

University Medical Center of Southern Nevada


1800 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Central Valley


3730 South Eastern Avenue
Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Summerlin Hospital Medical Center


657 Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Seven Hills


3175 Saint Rose Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada-Pahrump


2340 East Calvada Boulevard
Suite 7 Pahrump, NV 89048
Map

702-384-0013
research@sncrf.org

Desert West Surgery


1111 Shadow Lane
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Charleston


2300 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013

Hope Cancer Care of Nevada


6827 West Tropicana Avenue
Suite 110 Las Vegas, NV 89103
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Henderson


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

University Cancer Center


3131 La Canada Street
Suite 231 Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Alliance for Childhood Diseases/Cure 4 the Kids Foundation


One Breakthrough Way
Las Vegas, NV 89135
Map

702-384-0013
research@sncrf.org

Kingman Regional Medical Center


3269 Stockton Hill Road
Kingman, AZ 86401
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada


9280 West Sunset Road
Suite 100 Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Radiation Oncology Associates


6630 B South McCarran
Suite 18 Reno, NV 89509
Map

702-384-0013
research@sncrf.org

Ann M Wierman MD LTD


3150 Tenaya Way
Suite 200 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Horizon Ridge


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Las Vegas Urology - Cathedral Rock


7200 Cathedral Rock Drive
Suites 180 and 210 Las Vegas, NV 89128
Map


research@sncrf.org

Urology Specialists of Nevada - Central


2010 Wellness Way
Suite 200 Las Vegas, NV 89106
Map


research@sncrf.org

Urology Specialists of Nevada - Green Valley


58 North Pecos Road
Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Southwest


8410 West Warm Springs Road
Suite 10 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Northwest


3150 North Tenaya Way
Suite 165 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Green Valley


1701 North Green Valley Parkway
Suite 10C Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Pecos


9053 South Pecos Road
Suite 2900 Las Vegas, NV 89074
Map


research@sncrf.org

Las Vegas Prostate Cancer Center


7150 West Sunset Road
Suite 100 Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Urology - Sunset


7150 West Sunset Road
Suite 201A and 202B Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Urology - Pebble


8915 South Pecos Road
Suite 19A Henderson, NV 89074
Map


research@sncrf.org

Valley Medical Center


400 South 43rd Street
Renton, WA 98055
Map

425-228-3440
research@valleymed.org