Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer
Condition: Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7
MeSH terms: Papillomavirus Infections; Carcinoma; Adenocarcinoma; Uterine Cervical Neoplasms; Recurrence
Intervention: Ipilimumab; Laboratory Biomarker Analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well ipilimumab works in treating patients with human
      papilloma virus (HPV)-related cervical cancer that has come back or that has spread to other
      areas of the body. Monoclonal antibodies, such as ipilimumab, can find tumor cells and help
      kill them or carry tumor-killing substances to them.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic or recurrent
             cervical cancer of squamous, adenocarcinoma or mixed histology type not suited to
             definitive localized therapy; HPV status will be confirmed for all patients following
             enrollment

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as > 10 mm with computed
             tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

          -  Previous therapy:

               -  Patients may have undergone surgery and/or received definitive radiation or
                  chemo-radiation for localized disease in the past

               -  Radiation treatment with curative intent (radical chemoradiotherapy or adjuvant
                  chemoradiotherapy) must have been completed >= 3 months prior to enrollment

                    -  Note: patients who completed palliative radiation therapy 2 weeks before
                       start of ipilimumab are allowed as long as this does not affect measurable
                       disease

               -  Patients must have been exposed to platinum chemotherapy either as part of
                  definitive chemo-radiation OR as first line systemic treatment for metastatic
                  disease

               -  Patients MAY have received up to two prior lines of systemic chemotherapy for
                  metastatic or recurrent disease; patients with metastatic disease at first
                  presentation MUST have received one platinum based line of chemotherapy

               -  All chemotherapy must have been completed >= 4 weeks prior to enrollment with
                  radiologic evidence of radiological disease progression

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Life expectancy of greater than 3 months

          -  Leukocytes >= 3.0 x 10^9/L

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Total bilirubin within normal institutional limits (except in Gilbert's syndrome)

          -  Thyroid stimulating hormone (TSH) =< upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine < 1.25 ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 as calculated by
             the Cockcroft and Gault formula

          -  All radiology studies must be performed =< 3 weeks prior to the start of therapy

          -  Subjects with treated and asymptomatic brain metastases are eligible; patients that
             received palliative radiation (for brain metastases) are eligible if they have been
             asymptomatic for at least 2 weeks with use of maintenance steroid therapy, and last
             received radiation at least 4 weeks prior to start of therapy

          -  Ability to understand and willing to sign a written informed consent document

          -  Ongoing prior toxicities related to previous treatments must be recovered to =< grade
             1 at the time of registration (with the exception of alopecia or skin depigmentation)

          -  Patients are willing to undergo tumor biopsy pre-treatment (within 14 days prior to
             registration) and post-treatment (within the first week of cycle 2 onset); patients
             who consent but have tumor that is not amenable to safe biopsy will be allowed to
             enter the trial/continue therapy as per protocol if this has been addressed and
             permission is granted from the lead consortium principal investigator (PI) prior to
             registration continuation of treatment

        Exclusion Criteria:

          -  Patients who have had chemotherapy < 4 weeks prior to enrollment (< 6 weeks for
             nitrosoureas or mitomycin C) or who had radiation therapy with curative intent < 3
             months prior to enrollment (< 2 weeks for palliative radiation therapy) or those who
             have not recovered (=< grade 1) from adverse events related to previous treatments are
             excluded

          -  Patients with a history of prior treatment with ipilimumab or other cytotoxic
             T-lymphocyte antigen 4 (CTLA4) agonists or antagonists, anti-programmed death 1 (PD 1)
             antibody, cluster of differentiation (CD)137 agonist or other immune activating
             therapy such as anti-CD 40 antibody are excluded

          -  Patients who are receiving any other investigational agents

          -  Autoimmune disease: patients with a history of inflammatory bowel disease, including
             ulcerative colitis and Crohn's disease, are excluded from this study, as are patients
             with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
             vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor
             neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and
             Myasthenia Gravis, multiple sclerosis)

          -  Patients requiring immunosuppressive agents, unless required for treating potential
             immune related adverse effects; steroids at their lowest effective dose in patients
             with radiated brain metastases is permitted

          -  Patients with known immune impairment who may be unable to respond to anti-CTLA 4
             antibody

          -  Any other prior malignancy from which the patient has been disease free for less than
             3 years, with the exception of adequately treated and cured basal or squamous cell
             skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other
             cancer

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ipilimumab

          -  Patients requiring systemic steroids are excluded; narcotics should be used with
             caution

          -  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 chronic hepatitis B or hepatitis C infections should
             be excluded

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with ipilimumab

          -  Patients with active or chronic infection with human immunodeficiency virus (HIV) who
             have raised viral loads or uncontrolled disease are ineligible; those patients however
             who exhibit minimal viral loads with good control whilst on stable anti-viral regimen
             may be considered if they meet all other eligibility criteria