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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01711515
First received: October 18, 2012
Last updated: May 23, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified Positive Para-Aortic Lymph Node Positive Pelvic Lymph Node Stage IB2 Cervical Cancer Stage II Cervical Cancer Stage IIA Cervical Cancer Stage IIB Cervical Cancer Stage IIIB Cervical Cancer Stage IVA Cervical Cancer Drug: Cisplatin Radiation: External Beam Radiation Therapy Radiation: Internal Radiation Therapy Biological: Ipilimumab Other: Laboratory Biomarker Analysis Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Chronic toxicities experienced within one year of completion of therapy [ Time Frame: Up to 1 year post-treatment ]
  • Location of recurrence (loco-regional versus distant) [ Time Frame: Up to 1 year post-treatment ]
  • 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 ]
    Will be summarized using Kaplan-Meier plots.

  • Progression-free survival (PFS) [ Time Frame: From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment ]
    Will be summarized using Kaplan-Meier plots. Relationships of translational research endpoints to PFS will be explored if practical.

  • 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 ]
    Relationships of translational research endpoints to response will be explored if practical.


Other Outcome Measures:
  • Characterization of differential activated T-cell responses based on HLA-subtype A*0201 [ Time Frame: Up to 2 years ]
    Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.

  • Enumeration of HPV-specific T-cells [ Time Frame: Up to 2 years ]
    Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.

  • Kinetics of HPV-specific T-cell expansion [ Time Frame: Up to 2 years ]
    Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical.

  • Measurable parameters from the fludeoxyglucose F 18 (FDG)-PET/CT, including SUVmax of the primary tumor, metabolic tumor volume (MTV) if available, the presence of abnormal FDG uptake within lymph nodes [ Time Frame: Up to 2 years ]
    Summary statistics (and graphs) of translational research endpoints will be done by dose level. Relationships of these endpoints to response and PFS will be explored if practical. Within-patient changes in the FDG-PET/CT SUVmax and MTV (if available) will be examined.


Enrollment: 34
Actual Study Start Date: October 1, 2012
Primary Completion Date: March 9, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: External Beam Radiation Therapy
Undergo external beam radiation therapy
Other Names:
  • Definitive Radiation Therapy
  • EBRT
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
Radiation: Internal Radiation Therapy
Undergo intracavitary brachytherapy
Other Names:
  • BRACHYTHERAPY
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01711515

Locations
United States, California
Los Angeles County-USC Medical Center
Los Angeles, California, United States, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
The Hospital of Central Connecticut
New Britain, Connecticut, United States, 06050
United States, Georgia
Augusta University Medical Center
Augusta, Georgia, United States, 30912
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87102
United States, New York
Montefiore Medical Center-Einstein Campus
The Bronx, New York, United States, 10461
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Rhode Island
Women and Infants Hospital
Providence, Rhode Island, United States, 02905
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jyoti Mayadev NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01711515     History of Changes
Other Study ID Numbers: NCI-2012-01733
NCI-2012-01733 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
GOG-9929
GOG-PIS1102
GOG-9929 ( Other Identifier: NRG Oncology )
GOG-9929 ( Other Identifier: CTEP )
U10CA180868 ( US NIH Grant/Contract Award Number )
U10CA027469 ( US NIH Grant/Contract Award Number )
Study First Received: October 18, 2012
Last Updated: May 23, 2017

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Cisplatin
Antibodies, Monoclonal
Succinylcholine
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Neuromuscular Depolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on June 21, 2017