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
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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
DLTs occurring during adjuvant ipilimumab in the dose escalation phase
During first 2 courses of treatment
Gynecologic Oncology Group
United States: Food and Drug Administration
|Hartford Hospital||Hartford, Connecticut 06102-5037|
|University of Oklahoma Health Sciences Center||Oklahoma City, Oklahoma 73104|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Thomas Jefferson University Hospital||Philadelphia, Pennsylvania 19131|
|University of Southern California||Los Angeles, California 90033|
|The Hospital of Central Connecticut||New Britain, Connecticut 06050|
|University of California Medical Center At Irvine-Orange Campus||Orange, California 92868|
|Women and Infants Hospital||Providence, Rhode Island 02905|