Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01693783
First received: September 21, 2012
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This phase II trial studies how well giving ipilimumab works in treating patients with human papilloma virus (HPV)-related cervical cancer that has come back or that has spread to other areas of the body. Monoclonal antibodies, such as ipilimumab, can find tumor cells and help kill them or carry tumor-killing substances to them.


Condition Intervention Phase
Cervical Adenocarcinoma
Cervical Squamous Cell Carcinoma
Human Papilloma Virus Infection
Recurrent Cervical Cancer
Stage IVA Cervical Cancer
Stage IVB Cervical Cancer
Biological: ipilimumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Ipilimumab in Women With Metastatic or Recurrent HPV-Related Cervical Carcinoma of Either Squamous Cell or Adenocarcinoma Histologies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Frequency and severity of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.


Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ] [ Designated as safety issue: No ]
    Computed using the Kaplan-Meier method.

  • Antitumor activity (partial response [PR], complete response [CR], and stable disease [SD]) using immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary statistics, such as mean, median, counts and proportion, will be used.

  • Predictive value of baseline C-reactive protein [ Time Frame: Up to week 3 of course 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: December 2012
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ipilimumab)
Patients receive ipilimumab IV over 90 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving objective response or stable disease continue to receive maintenance therapy comprising ipilimumab IV over 90 minutes once every 12 weeks. Maintenance treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
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

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety of ipilimumab in eligible patients with recurrent or metastatic cervical cancer.

II. To assess the antitumor activity of ipilimumab in eligible patients with recurrent or metastatic cervical cancer via assessment of objective response rates (ORR).

SECONDARY OBJECTIVES:

I. To assess the antitumor activity of ipilimumab through secondary endpoints including of disease stabilization and progression free survival (PFS).

II. Assessment of antitumor activity of ipilimumab using immune-related response criteria (irRC) III. Assessment of the predictive value of baseline C-reactive protein. IV. Assess the biologic responses of exposure to ipilimumab via correlative studies involving analysis of lymphocyte subsets and assessment of cervical cancer-antigen specific T cells anti-tumor response.

V. Evaluation of archival tissue with regard to markers of immune population in correlation with clinical stage and response to treatment.

OUTLINE:

Patients receive ipilimumab intravenously (IV) over 90 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving objective response or stable disease continue to receive maintenance therapy comprising ipilimumab IV over 90 minutes once every 12 weeks. Maintenance treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up 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 must have histologically or cytologically confirmed metastatic or recurrent HPV-related cervical cancer of squamous, adenocarcinoma or mixed histology type not suited to definitive localized therapy
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Previous therapy:

    • Patients may have undergone surgery and/or received definitive radiation or chemo-radiation for localized disease in the past
    • Radiation treatment must have been completed >= 3 months prior to enrollment
    • Patients must have been exposed to platinum chemotherapy either as part of definitive chemo-radiation OR as first line systemic treatment for metastatic disease
    • Patients MAY have received up to two prior lines of systemic chemotherapy for metastatic or recurrent disease; patients with metastatic disease at first presentation MUST have received one platinum based line of chemotherapy
    • All chemotherapy must have been completed >= 4 weeks prior to enrollment with radiologic evidence of radiological disease progression
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3.0 x 10^9/L
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Total bilirubin within normal institutional limits (except in Gilbert's syndrome)
  • Thyroid stimulating hormone (TSH) within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine < 1.25 x upper limit of normal (ULN) OR creatinine clearance >= 50mL/min/1.73 m^2 as calculated by the Cockroft and Gault formula
  • All radiology studies must be performed =< 3 weeks prior to the start of therapy
  • Subjects with treated and asymptomatic brain metastases are eligible; patients that received palliative radiation (for brain metastases) are eligible if they do not require maintenance steroid treatment, have been asymptomatic for at least 2 weeks following cessation of steroid therapy, and last received radiation at least 4 weeks prior to start of therapy
  • Ability to understand and willing to sign a written informed consent document
  • Ongoing prior toxicities related to previous treatments must be recovered to < grade 1 at the time of registration (with the exception of alopecia or skin depigmentation)
  • Patients are willing to undergo tumor biopsy pre-treatment (7 days prior to registration) and post-treatment (within the first week of cycle 2 onset); patients who consent but have tumor that is not amenable to safe biopsy will be allowed to enter the trial/continue therapy as per protocol if this has been addressed and permission is granted from the lead consortium principal investigator (PI) prior to registration continuation of treatment

Exclusion Criteria:

  • Patients who have had chemotherapy < 4 weeks prior to enrollment (< 6 weeks for nitrosoureas or mitomycin C) or who had radiation < 3 months prior to enrollment or those who have not recovered (< grade 1) from adverse events related to previous treatments are excluded
  • Patients with a history of prior treatment with Ipilimumab or other cytotoxic T-lymphocyte antigen 4 (CTLA4) agonists or antagonists, anti-programmed death 1 (PD 1) antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded
  • 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 requiring immunosuppressive agents, unless required for treating potential immune related adverse effects; steroids at their lowest effective dose in patients with radiated brain metastases is permitted
  • Patients with known immune impairment who may be unable to respond to anti-CTLA 4 antibody
  • Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab
  • Patients requiring systemic steroids are excluded, as these drugs may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose; narcotics should be used with caution as they may mask the signs and symptoms of serious gastrointestinal immune-related adverse events (irAEs) including intestinal perforation
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with chronic hepatitis B or hepatitis C infections should be excluded because of potential effects on immune function and/ or drug interactions
  • Pregnant women are excluded from this study because ipilimumab is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ipilimumab, breastfeeding should be discontinued if the mother is treated with ipilimumab
  • Patients with active or chronic infection with human immunodeficiency virus (HIV) who have raised viral loads or uncontrolled disease are ineligible because of the potential for anticipated and unknown adverse immune related effects secondary to treatment with ipilimumab; those patients however who exhibit minimal viral loads with good control whilst on stable anti-viral regimen may be considered if they meet all other eligibility criteria
  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: NCT01693783

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Mihaela C. Cristea    626-256-4673    mcristea@coh.org   
Principal Investigator: Mihaela C. Cristea         
University of Southern California/Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Lynda D. Roman    323-865-0451    lroman@usc.edu   
Principal Investigator: Lynda D. Roman         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Edwin A. Alvarez    916-734-6900    edwin.alvarez@ucdmc.ucdavis.edu   
Principal Investigator: Edwin A. Alvarez         
City of Hope South Pasadena Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    Skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Gini F. Fleming    773-702-6712    gfleming@medicine.bsd.uchicago.edu   
Principal Investigator: Gini F. Fleming         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Lainie P. Martin    215-728-3889    lainie.Martin@fccc.edu   
Principal Investigator: Lainie P. Martin         
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Prafull Ghatage    403-521-3721    Prafull.Ghatage@albertahealthservices.ca   
Principal Investigator: Prafull Ghatage         
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Katia S. Tonkin    780-432-8514    katia.tonkin@albertahealthservices.ca   
Principal Investigator: Katia S. Tonkin         
Canada, British Columbia
BC Cancer Research Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 1L3
Contact: Anna Tinker    604-877-6000    atinker@bccancer.bc.ca   
Principal Investigator: Anna Tinker         
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Holger W. Hirte    905-387-9495    hal.hirte@jcc.hhsc.ca   
Principal Investigator: Holger W. Hirte         
Cancer Centre of Southeastern Ontario at Kingston General Hospital Recruiting
Kingston, Ontario, Canada, K7L 5P9
Contact: James J. Biagi    613-544-2630    jim.biagi@krcc.on.ca   
Principal Investigator: James J. Biagi         
London Regional Cancer Program Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Stephen A. Welch    519-685-8640    stephen.welch@lhsc.on.ca   
Principal Investigator: Stephen A. Welch         
Ottawa General Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Johanne I. Weberpals    613-737-8899ext76462    jweberpals@ottawahospital.on.ca   
Principal Investigator: Johanne I. Weberpals         
University Health Network-Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Amit M. Oza    416-946-2818    amit.oza@uhn.ca   
Principal Investigator: Amit M. Oza         
Sponsors and Collaborators
Investigators
Principal Investigator: Amit Oza Princess Margaret Hospital Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01693783     History of Changes
Other Study ID Numbers: NCI-2012-02877, NCI-2012-02877, PHL-085, 9209, N01CM00071, N01CM00038, N01CM00032
Study First Received: September 21, 2012
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Uterine Cervical Neoplasms
Papilloma
Virus Diseases
Warts
Papillomavirus Infections
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
DNA Virus Infections
Skin Diseases, Viral
Tumor Virus Infections
Skin Diseases, Infectious
Skin Diseases
Antibodies, Monoclonal
Cytotoxic T-lymphocyte antigen 4
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 20, 2014