Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer
This phase I trial studies the side effects and best dose of ipilimumab given after chemoradiation therapy in treating patients with locally advanced cervical cancer. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving ipilimumab together with chemoradiation therapy may be a better way to block cancer growth.
Cervical Adenosquamous Cell Carcinoma
Cervical Squamous Cell Carcinoma
Stage IB Cervical Cancer
Stage IIA Cervical Cancer
Stage IIB Cervical Cancer
Stage IIIB Cervical Cancer
Stage IVA Cervical Cancer
Radiation: external beam radiation therapy
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A PHASE I TRIAL OF SEQUENTIAL IPILIMUMAB AFTER CHEMORADIATION FOR THE PRIMARY TREATMENT OF PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER STAGES IB2/IIA WITH POSITIVE PARA-AORTIC LYMPH NODES ONLY AND STAGE IIB/IIIB/IVA WITH POSITIVE LYMPH NODES|
- DLTs occurring during adjuvant ipilimumab in the dose escalation phase [ Time Frame: During first 2 courses of treatment ] [ Designated as safety issue: Yes ]
- DLTs occurring in the feasibility phase [ Time Frame: Over 4 courses of treatment ] [ Designated as safety issue: Yes ]
- Toxicities as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: Up to 2 years post-treatment ] [ Designated as safety issue: Yes ]
- Response rate in patients enrolled with measurable disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 2 years post-treatment ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment ] [ Designated as safety issue: No ]Will be summarized using Kaplan-Meier plots.
- Overall survival [ 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 ] [ Designated as safety issue: No ]Will be summarized using Kaplan-Meier plots.
- Location of recurrence (loco-regional versus distant) [ Time Frame: Up to 1 year post-treatment ] [ Designated as safety issue: No ]
- Chronic toxicities experienced within one year of completion of therapy [ Time Frame: Up to 1 year post-treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2012|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cisplatin, radiation therapy, and ipilimumab)
Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended 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.
Other Names:Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRTRadiation: brachytherapy
Undergo intracavitary brachytherapy
Other Names:Biological: ipilimumab
Other Names:Other: laboratory biomarker analysis
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.
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.
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.
|United States, California|
|University of Southern California||Recruiting|
|Los Angeles, California, United States, 90033-0804|
|Contact: Yvonne G. Lin-Liu 323-865-0451|
|Principal Investigator: Yvonne G. Lin-Liu|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Robert S. Mannel 405-271-4272 firstname.lastname@example.org|
|Principal Investigator: Robert S. Mannel|
|United States, Rhode Island|
|Women and Infants Hospital||Recruiting|
|Providence, Rhode Island, United States, 02905|
|Contact: Cara A. Mathews 401-274-1122 email@example.com|
|Principal Investigator: Cara A. Mathews|
|Principal Investigator:||Yvonne Lin-Liu||Gynecologic Oncology Group|