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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 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: July 11, 2014
Last verified: March 2014

October 18, 2012
July 11, 2014
October 2012
July 2014   (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 ] [ 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 ]
  • DLTs occurring in the first two cycles of adjuvant ipilimumab in the dose escalation phase [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: Yes ]
  • DLTs occurring in the four cycles of adjuvant ipilimumab in the feasibility phase [ Time Frame: Up to 12 weeks ] [ 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 ]
Complete list of historical versions of study NCT01711515 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced 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 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.

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
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cervical Adenocarcinoma
  • 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
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Radiation: external beam radiation therapy
    Undergo external beam radiation therapy
    Other Name: EBRT
  • Radiation: brachytherapy
    Undergo intracavitary brachytherapy
    Other Names:
    • low-LET implant therapy
    • radiation brachytherapy
    • therapy, low-LET implant
  • Biological: ipilimumab
    Given IV
    Other Names:
    • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
    • MDX-010
    • MDX-CTLA-4
    • monoclonal antibody CTLA-4
  • 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: brachytherapy
  • 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.
 
Recruiting
18
Not Provided
July 2014   (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 glutamic 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-PD 1 antibody, CD137 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
Female
18 Years and older
No
United States
 
NCT01711515
NCI-2012-01733, NCI-2012-01733, GOG-9929, GOG-9929, U10CA027469
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Yvonne Lin-Liu Gynecologic Oncology Group
National Cancer Institute (NCI)
March 2014

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