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Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02635360
Recruitment Status : Recruiting
First Posted : December 18, 2015
Last Update Posted : February 26, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Linda R Duska, University of Virginia

Tracking Information
First Submitted Date  ICMJE December 4, 2015
First Posted Date  ICMJE December 18, 2015
Last Update Posted Date February 26, 2020
Study Start Date  ICMJE January 2016
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2015)
  • Change in immunologic markers following combination of study drug with chemoradiation [ Time Frame: At 6 weeks of chemoradiation and 12 weeks post-chemoradiation ]
    Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared.
  • Incidence of dose limiting toxicities [ Time Frame: From start of treatment until 12 weeks post-chemoradiation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2015)
  • Metabolic Response Rate on PET/CT imaging [ Time Frame: 12 weeks after chemotherapy ]
  • Incidence of distant metastases [ Time Frame: From start of treatment until up to 5 years following end of treatment ]
  • Progression Free Survival [ Time Frame: From start of treatment until up to 5 years following end of treatment ]
  • Overall Survival [ Time Frame: From start of treatment until up to 5 years following end of treatment ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer
Official Title  ICMJE A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
Brief Summary The purpose of this study is to evaluate the safety and effectiveness of immunotherapy in combination with chemotherapy and radiation (chemoradiation) for the treatment of advanced cervical cancer. Pembrolizumab, a type of immunotherapy called a checkpoint inhibitor, will be administered after or during chemoradiation.
Detailed Description

Primary: (1) To estimate the immunologic effects, as assessed in the tumor & PBMC, of both sequential and concurrent administration of pembrolizumab to CRT. Change between pre and post measurements of HPV E2, E7 specific CD8+ T cells, regulatory FoxP3+ T cells (Tregs) and the ratio of CD8+ T cells to Tregs are the immune measurements of primary interest. (2) To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer. Secondary: (1) To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT.

(2) To estimate rates of distant metastasis as the first site of recurrence for patients.

(3) To estimate the influence of concurrent and consolidative MK-3475 on levels of plasminogen activator inhibitor-1 (PAI-1), a marker of immunosuppressive TGF-B.

(4) To estimate the influence of concurrent and consolidative MK-3475 on levels of IDO, an enzyme that depletes tryptophan, which is essential for T-cell function.

(5) To estimate the influence of concurrent and consolidative MK-3475 on levels of MHC class I (CD8+ T cell ligand) and MICA (NK ligand), as measured by MHC.

(6) To estimate the progression free survival (PFS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT.

(7) To estimate the overall survival (OS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cervical Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months.
    Other Names:
    • Keytruda
    • MK-3475
  • Radiation: Brachytherapy
    Radiation is done for standard clinical care purposes.
    Other Name: chemoradiation
  • Drug: Cisplatin
    40 mg of chemotherapy drug will be given weekly for 5-6 weeks.
    Other Name: chemotherapy
Study Arms  ICMJE
  • Experimental: Following chemoradiation
    Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab.
    Interventions:
    • Drug: Pembrolizumab
    • Radiation: Brachytherapy
    • Drug: Cisplatin
  • Experimental: Concurrent to chemoradiation
    Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab.
    Interventions:
    • Drug: Pembrolizumab
    • Radiation: Brachytherapy
    • Drug: Cisplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 15, 2015)
88
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed cervical cancer.
  • Must have adequate organ function.

Exclusion Criteria:

  • Subject is pregnant.
  • Recurrent cervical cancer.
  • Distant metastases.
  • Malignancy within the last 5 years; basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy is permissable.
  • Subject has had prior radiation, chemotherapy, targeted therapy, or investigational therapy for cervical cancer.
  • Subject has a immunodeficiency.
  • Known history of HIV, Hepatitis B, Hepatitis C, TB, or inflammatory bowel disease.
  • Hypersensitivity to pembrolizumab or similar drugs.
  • Subject has an active autoimmune disease in the past 2 years.
  • Known history of non-infectious pneumonitis.
  • Subject has an active infection.
  • Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases are permissible. Talk to Study Contact for specifics.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: April M Muniz, MSHS 434-243-5350 am4pf@virginia.edu
Contact: Linda Duska lduska@virginia.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02635360
Other Study ID Numbers  ICMJE 18472
UVA-LACC-PD201 ( Other Grant/Funding Number: Merck Sharp & Dohme Corp. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Linda R Duska, University of Virginia
Study Sponsor  ICMJE Linda R Duska
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Linda Duska, MD University of Virginia
PRS Account University of Virginia
Verification Date February 2020

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