The MetroHealth System

Conditions

• 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

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

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 caregiver and/or family member
available will also be considered eligible

- 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)

- Patients must agree to not receive live vaccines while on this study

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved progression-free survival (PFS) versus systemic chemotherapy alone. SECONDARY OBJECTIVES: I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved overall survival (OS) versus systemic chemotherapy alone. II. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved objective response using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 versus systemic chemotherapy alone. III. To evaluate toxicity profiles of the two regimens. IV. To elucidate the role of the human papillomavirus (HPV) circulating cell-free deoxyribonucleic acid (cfDNA) viral load on PFS with the hypothesis that longer PFS will be associated with viral load. OUTLINE: Patients are randomized to 1 of 2 arms. Randomization will be 2:1 favoring the experimental regimen, Arm B. ARM A: Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1 month, then every 3 months for 2 years.