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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: September 4, 2017
Last verified: April 2017
October 18, 2012
September 4, 2017
October 1, 2012
March 9, 2017   (Final data collection date for primary outcome measure)
  • 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 ]
  • DLTs occurring in the first two cycles of adjuvant ipilimumab in the dose escalation phase [ Time Frame: Up to 6 weeks ]
  • DLTs occurring in the four cycles of adjuvant ipilimumab in the feasibility phase [ Time Frame: Up to 12 weeks ]
  • Toxicities as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: Up to 2 years post-treatment ]
Complete list of historical versions of study NCT01711515 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
  • 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 ]
    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 ]
    Will be summarized using Kaplan-Meier plots.
  • 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 ]
  • 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.
Not Provided
 
Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer
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
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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
    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
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.
Interventions:
  • Drug: Cisplatin
  • Radiation: External Beam Radiation Therapy
  • Radiation: Internal Radiation Therapy
  • Biological: Ipilimumab
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
34
Not Provided
March 9, 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01711515
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 )
U10CA180830 ( U.S. NIH Grant/Contract )
U10CA180868 ( U.S. NIH Grant/Contract )
U10CA027469 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jyoti Mayadev NRG Oncology
National Cancer Institute (NCI)
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP