Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer
Condition: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7
MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Recurrence
Intervention: Laboratory Biomarker Analysis; Nivolumab
Intervention description: Correlative studies; Given IV
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well nivolumab works in treating
      patients with cervical cancer that has grown, come back, or spread to other places in the
      body. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by
      targeting certain cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have persistent, recurrent or metastatic squamous cell carcinoma,
             adenosquamous carcinoma or adenocarcinoma of the cervix with documented disease
             progression (disease not amendable to curative therapy); NOTE: the following cervical
             tumors are not eligible: minimal deviation/adenoma malignum, gastric type
             adenocarcinoma, clear cell carcinoma and mesonephric carcinoma; histologic
             confirmation of the original primary tumor is required via the pathology report

          -  All patents must have measurable disease as defined by RECIST 1.1; measurable disease
             is defined as at least one lesion that can be accurately measured in at least one
             dimension (longest diameter to be recorded); each lesion must be >= 10 mm when
             measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper
             measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes
             must be >= 15 mm in short axis when measured by CT or MRI

          -  Patients must have at least one "target" lesion" to be used to assess response on this
             protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be
             designated as "non-target" lesions unless progression is documented or a biopsy is
             obtained to confirm persistence at least 90 days following completion of radiation
             therapy

          -  Appropriate for study entry based on the following diagnostic workup:

               -  History/physical examination within 28 days prior to registration

               -  Imaging of target lesion(s) within 28 days prior to registration

               -  Further protocol-specific assessments:

                    -  Recovery from adverse effects of recent surgery, radiotherapy or
                       chemotherapy

                    -  Any other prior therapy directed at the malignant tumor including
                       chemotherapy, biologic/targeted agents and immunologic agents must be
                       discontinued at least three weeks prior to registration

                    -  Investigation agents must be discontinued for at least 30 days prior to
                       registration

                    -  Any prior radiation therapy must be completed at least 4 weeks prior to
                       registration

                    -  At least 4 weeks must have elapsed since any major surgery prior to
                       registration

          -  Patients must have had one prior systemic chemotherapeutic regimen for management of
             persistent, recurrent or metastatic carcinoma of the cervix (e.g.;
             paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab); chemotherapy administered
             concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a
             systemic chemotherapy regimen; adjuvant chemotherapy given following the completion of
             radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as
             a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles);
             NOTE: patients who have received more than one prior regimen are NOT eligible

          -  Performance status of 0 or 1

          -  Absolute neutrophil count (ANC) >= 1,500/ul

          -  Platelets >= 100,000/ul

          -  Creatinine =< 1.5 x institutional upper limit of normal (ULN) or creatinine clearance
             (CrCl) >= 40 mL/min using Cockcroft-Gault formula

          -  Bilirubin =< 1.5 x ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

          -  Normal thyroid function testing (thyroid stimulating hormone [TSH]) within 14 days
             prior to registration

          -  The patient or a legally authorized representative must provide study-specific
             informed consent authorization permitting release of personal health information prior
             to study entry

        Exclusion Criteria:

          -  Patients who have had prior therapy with nivolumab or with an anti-PD-1,
             anti-PD-ligand (L)1, anti-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 check point pathways

          -  History of severe hypersensitivity reaction to any monoclonal antibody

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years

          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
             or active infection, symptomatic congestive heart failure and unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements

          -  Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) 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; WOCBP
             should use an adequate method to avoid pregnancy for 23 weeks after the last dose of
             investigational drug; WOCBP must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IV/L or equivalent units of human chorionic gonadotropin
             [HCG]) within 24 hours prior to the start of nivolumab; women must not be
             breastfeeding

               -  Women who are not of childbearing potential (i.e., who are postmenopausal or
                  surgically sterile or have undergone definitive radiation) do not require
                  contraception

               -  Women of childbearing potential (WOCBP) is defined as any female who has
                  experienced menarche and who has not undergone surgical sterilization
                  (hysterectomy of bilateral oophorectomy) or who is not postmenopausal; menopause
                  is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of
                  other biological or physiological causes; in addition, women under the age of 55
                  must have a documented serum follicle stimulating hormone (FSH) level greater
                  than 40 mIU/mL

               -  WOCBP receiving nivolumab will be instructed to adhere to contraception for a
                  period of 23 weeks after the last dose of investigational product

               -  Should a woman become pregnant or suspect she is pregnant while she is
                  participating in this study, she should inform the treating physician immediately

          -  Patients with known brain metastases or leptomeningeal metastases are excluded unless
             the following conditions are met:

               -  Metastases have been treated and there is no magnetic resonance imaging (MRI)
                  evidence of progression for at least 4 weeks after treatment is complete (must be
                  confirmed 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

          -  Patients should be excluded if they have known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

               -  Patients should be excluded if they have a positive test for hepatitis B virus
                  surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody)
                  indicating acute or chronic infection

          -  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 systemic corticosteroids, 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 (IRB), Crohn's,
             ulcerative colitis, hepatitis; and patients with a history of toxic epidermal
             necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be
             excluded; patient with vitiligo, endocrine deficiencies including thyroiditis managed
             with replacement hormones including physiologic corticosteroids are eligible; patients
             with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis
             controlled with topical medication and patients with positive serology, such as
             antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the
             presence of target organ involvement and potential need for systemic treatment but
             should otherwise be eligible

               -  NOTE: patients are permitted to enroll if they have vitiligo, type I diabetes
                  mellitus, residual hypothyroidism due to autoimmune condition only requiring
                  hormone replacement, psoriasis not requiring systemic treatment, or conditions
                  not expected to recur in the absence of an external trigger (precipitating event)

          -  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

          -  Patients who have had evidence of active or acute diverticulitis, intra-abdominal
             abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI)
             obstruction and/or who require parenteral hydration and/or nutrition