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.
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of adjuvant ipilimumab following concurrent weekly cisplatin and extended field radiation in women with newly diagnosed locally advanced cervical cancer stage IB2/ IIA with-positive para-aortic lymph nodes only and stage IIB/IIIB/IVA with positive lymph nodes. II. To determine the feasibility of the treatment regimen over the four cycles of adjuvant ipilimumab once the MTD is estimated. III. To assess the toxicities of the treatment regimen per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. SECONDARY OBJECTIVES: I. To examine progression free survival for 1 year after study completion. II. To determine site of recurrence, loco-regional versus distant, for one year after completion of therapy. III. To estimate the frequency of chronic toxicities experienced within one year after completion of therapy. TERTIARY OBJECTIVES: I. To enumerate the human papillomavirus (HPV)-subtype-specific T-cells and characterize the kinetics of HPV-subtype-specific T-cell expansion associated with chemoradiation and ipilimumab treatment. II. To characterize the association between differential expression of immune markers on leukocytes from human leukocyte antigen (HLA)-A\*0201 patients and response to chemoradiation and ipilimumab treatment. III. To assess qualitative changes in maximum standardized uptake value (SUVmax) from positron emission tomography (PET)/computed tomography (CT) after treatment with chemoradiation and ipilimumab. IV. To bank residual plasma (obtained from leukocyte processing) for future research. OUTLINE: This is a dose-escalation study of ipilimumab. Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo external beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Given IV
Undergo external beam radiation therapy
Undergo intracavitary brachytherapy
Given IV
Correlative studies
Los Angeles County-USC Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Hartford Hospital
Hartford, Connecticut, United States
The Hospital of Central Connecticut
New Britain, Connecticut, United States
Augusta University Medical Center
Augusta, Georgia, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
...and 6 more locations
DLTs occurring during adjuvant ipilimumab in the dose escalation phase
Time frame: During first 2 courses of treatment
DLTs occurring in the feasibility phase
Time frame: Over 4 courses of treatment
Toxicities as assessed by CTCAE version 4
Time frame: Up to 2 years post-treatment
Response rate in patients enrolled with measurable disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Relationships of translational research endpoints to response will be explored if practical.
Time frame: Up to 2 years post-treatment
Progression-free survival (PFS)
Will be summarized using Kaplan-Meier plots. Relationships of translational research endpoints to PFS will be explored if practical.
Time frame: From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment
Overall survival
Will be summarized using Kaplan-Meier plots.
Time frame: From time of study entry to time of death or the date the patient was last confirmed to be alive, assessed up to 1 year post-treatment
Location of recurrence (loco-regional versus distant)
Time frame: Up to 1 year post-treatment
Chronic toxicities experienced within one year of completion of therapy
Time frame: Up to 1 year post-treatment
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