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Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

Sponsor
Linda R Duska (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02635360
Collaborator
Merck Sharp & Dohme LLC (Industry)
88
Enrollment
8
Locations
2
Arms
71
Duration (Months)
11
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
88 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
Study Start Date :
Jan 1, 2016
Actual Primary Completion Date :
Jan 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

Arm Intervention/Treatment
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.

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 Names:
  • chemoradiation

    • Drug: Cisplatin
    40 mg of chemotherapy drug will be given weekly for 5-6 weeks.
    Other Names:
  • chemotherapy

    		•
    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.

    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 Names:
  • chemoradiation

    • Drug: Cisplatin
    40 mg of chemotherapy drug will be given weekly for 5-6 weeks.
    Other Names:
  • chemotherapy

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in immunologic markers following combination of study drug with chemoradiation [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.

    2. Incidence of dose limiting toxicities [From start of treatment until 12 weeks post-chemoradiation]

    Secondary Outcome Measures

    1. Metabolic Response Rate on PET/CT imaging [12 weeks after chemotherapy]

    2. Incidence of distant metastases [From start of treatment until up to 5 years following end of treatment]

    3. Progression Free Survival [From start of treatment until up to 5 years following end of treatment]

    4. Overall Survival [From start of treatment until up to 5 years following end of treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of South Alabama Mitchell Cancer Institute Mobile Alabama United States 36604
    2 Johns Hopkins Baltimore Maryland United States 21287
    3 Washington University, School of Medicine Saint Louis Missouri United States 63108
    4 Levine Cancer Institute Charlotte North Carolina United States 28204
    5 University of Oklahoma Oklahoma City Oklahoma United States 73104
    6 University of Virginia Charlottesville Virginia United States 22908
    7 INOVA Fairfax Hospital Falls Church Virginia United States 22042
    8 Virginia Commonwealth University Richmond Virginia United States 23298

    Sponsors and Collaborators

    • Linda R Duska
    • Merck Sharp & Dohme LLC

    Investigators

    • Principal Investigator: Linda Duska, MD, University of Virginia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Linda R Duska, Associate Professor, Division of Gynecology Oncology, University of Virginia
    ClinicalTrials.gov Identifier:
    NCT02635360
    Other Study ID Numbers:
    • 18472
    • UVA-LACC-PD201
    First Posted:
    Dec 18, 2015
    Last Update Posted:
    Apr 28, 2021
    Last Verified:
    Apr 1, 2021
    Keywords provided by Linda R Duska, Associate Professor, Division of Gynecology Oncology, University of Virginia
    advanced
    cervical cancer
    pembrolizumab
    chemoradiation
    immunotherapy
    Additional relevant MeSH terms:
    Uterine Cervical Neoplasms
    Pembrolizumab

    Study Results

    No Results Posted as of Apr 28, 2021