Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

• Status: Completed
• Trial end date: 2020-07-17
• Target enrollment: 0
• Participant gender: Female

Summary

This phase I trial studies the side effects and best dose of ipilimumab when given after chemoradiation therapy in treating patients with stages IB2-IIB or IIIB-IVA cervical cancer. Drugs used in chemotherapy, such as cisplatin, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as ipilimumab, may find tumor cells and help carry tumor-killing substances to them. Giving ipilimumab together with chemoradiation therapy may be a better way treat cervical cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Collaborator: NRG Oncology
• Treatments: Antibodies, Monoclonal; Cisplatin; Ipilimumab; Succinylcholine

Criteria

Inclusion Criteria:

• Patients with histologically confirmed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): International Federation of Gynecology and Obstetrics (FIGO) clinical stages IB2/IIA with positive para-aortic lymph nodes or FIGO clinical stages IIB/IIIB/IVA with positive pelvic and/or para-aortic lymph nodes; nodal status will be confirmed by PET/CT scan, fine needle biopsy, extra peritoneal biopsy, laparoscopic biopsy or lymphadenectomy

• Patients must have a Gynecologic Oncology Group (GOG) performance status of 0-1

• Absolute neutrophil count (ANC) >= 1,500/mcl

• Platelets >= 100,000/mcl

• Creatinine =< institutional upper limit normal (ULN); note: if creatinine > ULN, creatinine clearance must be > 50 mL/min

• Bilirubin =< 1.5 x ULN

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN

• Alkaline phosphatase =< 2.5 x ULN

• Neuropathy (sensory and motor) =< grade 1

• Patients with ureteral obstruction (i.e., hydronephrosis identified on CT imaging) must undergo stent or nephrostomy tube placement prior to study entry

• Patients must meet the pre-entry requirements specified

• Patients must have signed an approved informed consent and authorization permitting the release of personal health information

• Patients of child-bearing potential must have a negative serum pregnancy test prior to study entry (within 72 hours prior to initiation of study treatment) and be practicing an effective form of contraception; women should not breast-feed while on this study

• Patients must not be receiving any other investigational agent

• Patients should have an audiogram at baseline, and patients with pre-existing hearing loss or hearing loss during treatment should be assessed frequently during cisplatin therapy

Exclusion Criteria:

• Patients who have received previous pelvic or abdominal radiation, cytotoxic chemotherapy, or previous therapy of any kind for this malignancy or any pelvic or abdominal radiation for any prior malignancy

• Patients with active infection

• Patients who have circumstances that will not permit completion of this study or the required follow-up

• Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment prevents full delivery of this protocol therapy

• Patients who have undergone major surgery, excluding diagnostic biopsy, within 30 days (to allow for full recovery) prior to registration

• Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within 6 months of registration

• Patients with a history of prior treatment with ipilimumab, anti-programmed cell death (PD) 1 antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody

• 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 with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) antibody

• History of allergic reactions attributed to compounds of similar chemical or biologic composition ipilimumab or other agents used in study

• Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded