Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01711515
First received: October 18, 2012
Last updated: May 28, 2015
Last verified: January 2015
  Purpose

This phase I trial studies the side effects and best dose of ipilimumab when given after chemoradiation therapy in treating patients with cervical cancer that has spread to nearby tissue or lymph nodes. 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
Stage IB 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: 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

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 ] [ 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 CTCAE version 4 [ Time Frame: Up to 2 years post-treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Chronic toxicities experienced within one year of completion of therapy [ Time Frame: Up to 1 year post-treatment ] [ Designated as safety issue: Yes ]
  • Location of recurrence (loco-regional versus distant) [ Time Frame: Up to 1 year post-treatment ] [ Designated as safety issue: No ]
  • 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.

  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 28
Study Start Date: October 2012
Estimated Primary Completion Date: November 2015 (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
  • CISPLATIN
  • 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 Radiation Therapy
  • 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
  • Internal Radiation Therapy
  • Radiation Brachytherapy
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • IPILIMUMAB
  • 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
Genders 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 Recruiting
Los Angeles, California, United States, 90033
Contact: Huyen Q. Pham    323-865-0451      
Principal Investigator: Huyen Q. Pham         
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Huyen Q. Pham    323-865-0451      
Principal Investigator: Huyen Q. Pham         
UC Irvine Health/Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Krishnansu S. Tewari    714-456-6191    awallick@uci.edu   
Principal Investigator: Krishnansu S. Tewari         
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Jyoti S. Mayadev    916-734-3089      
Principal Investigator: Jyoti S. Mayadev         
United States, Connecticut
Hartford Hospital Active, not recruiting
Hartford, Connecticut, United States, 06102
The Hospital of Central Connecticut Active, not recruiting
New Britain, Connecticut, United States, 06050
United States, Georgia
Georgia Regents University Medical Center Recruiting
Augusta, Georgia, United States, 30912
Contact: Sharad A. Ghamande    706-721-1663    cancer@georgiahealth.edu   
Principal Investigator: Sharad A. Ghamande         
United States, New Mexico
University of New Mexico Active, not recruiting
Albuquerque, New Mexico, United States, 87106
United States, New York
Montefiore Medical Center-Einstein Campus Active, not recruiting
Bronx, New York, United States, 10461
United States, Ohio
Case Western Reserve University Active, not recruiting
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation Active, not recruiting
Cleveland, Ohio, United States, 44195
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Robert S. Mannel    405-271-4272    julie-traylor@ouhsc.edu   
Principal Investigator: Robert S. Mannel         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Gina M. Mantia Smaldone    215-728-4790      
Principal Investigator: Gina M. Mantia Smaldone         
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Russell J. Schilder    215-728-4790      
Principal Investigator: Russell J. Schilder         
United States, Rhode Island
Women and Infants Hospital Recruiting
Providence, Rhode Island, United States, 02905
Contact: Cara A. Mathews    401-274-1122      
Principal Investigator: Cara A. Mathews         
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center Recruiting
Richmond, Virginia, United States, 23298
Contact: Jori S. Carter    804-628-1939      
Principal Investigator: Jori S. Carter         
Sponsors and Collaborators
Investigators
Principal Investigator: Jyoti Mayadev NRG Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01711515     History of Changes
Other Study ID Numbers: NCI-2012-01733, NCI-2012-01733, GOG-PIS1102, GOG-9929, GOG-9929, U10CA180868, U10CA027469
Study First Received: October 18, 2012
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 29, 2015