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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 November 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: November 25, 2014
Last verified: November 2014
  Purpose

This phase II trial studies how well 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 Papillomavirus Infection
Recurrent Cervical Carcinoma
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:
  • Incidence 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.

  • Objective response rate using Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease stabilization [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary statistics, such as mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum test may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Progression free survival [ 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, complete response, and stable disease) using immune-related response criteria [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary statistics, such as mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum test may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Predictive value of baseline C-reactive protein [ Time Frame: Up to week 3 of course 4 ] [ Designated as safety issue: No ]
    Summary statistics, such as mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum test may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Biologic responses of exposure to ipilimumab by analysis of lymphocyte subsets and assessment of cervical cancer-antigen specific T cells anti-tumor response [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Summary statistics, such as mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum test may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.

  • Markers of immune population, evaluated in archival tissue [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Summary statistics, such as mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum test may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.


Estimated Enrollment: 44
Study Start Date: December 2012
Estimated Primary Completion Date: July 2015 (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 for 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: Ipilimumab
Given IV
Other Names:
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
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 for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 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 must have histologically or cytologically confirmed metastatic or recurrent cervical cancer of squamous, adenocarcinoma or mixed histology type not suited to definitive localized therapy; HPV status will be confirmed for all patients following enrollment
  • 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 > 10 mm with 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 with curative intent (radical chemoradiotherapy or adjuvant chemoradiotherapy) must have been completed >= 3 months prior to enrollment

      • Note: patients who completed palliative radiation therapy 2 weeks before start of ipilimumab are allowed as long as this does not affect measurable disease
    • 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) =< upper limit of normal (ULN)
  • 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 ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 as calculated by the Cockcroft 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 have been asymptomatic for at least 2 weeks with use of maintenance 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 (within 14 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 therapy with curative intent < 3 months prior to enrollment (< 2 weeks for palliative radiation therapy) 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; narcotics should be used with caution
  • 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
  • Pregnant women are excluded from this study; 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; 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 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@hrcc.on.ca   
Principal Investigator: Holger W. Hirte         
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, N01CM00038, N01CM00032, N01CM00071
Study First Received: September 21, 2012
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Papillomavirus Infections
DNA Virus Infections
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Tumor Virus Infections
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014