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Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

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ClinicalTrials.gov Identifier: NCT02635360
Recruitment Status : Recruiting
First Posted : December 18, 2015
Last Update Posted : November 17, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Linda R Duska, University of Virginia

Study Description
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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
Cervical Cancer Drug: Pembrolizumab Radiation: Brachytherapy Drug: Cisplatin 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arms and Interventions
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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 Name: chemoradiation

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

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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

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

Secondary Outcome Measures :
  1. Metabolic Response Rate on PET/CT imaging [ Time Frame: 12 weeks after chemotherapy ]
  2. Incidence of distant metastases [ Time Frame: From start of treatment until up to 5 years following end of treatment ]
  3. Progression Free Survival [ Time Frame: From start of treatment until up to 5 years following end of treatment ]
  4. Overall Survival [ Time Frame: From start of treatment until up to 5 years following end of treatment ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02635360


Contacts
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Contact: April M Muniz, MSHS 434-243-5350 am4pf@virginia.edu
Contact: Linda Duska lduska@virginia.edu

Locations
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United States, Alabama
University of South Alabama Mitchell Cancer Institute Recruiting
Mobile, Alabama, United States, 36604
Contact: Joanie Broemmelsiek    251-445-9866    jbroemmelsiek@health.southalabama.edu   
Contact: Renee Russell    251-445-9649    rwrussell@health.southalabama.edu   
Principal Investigator: Jennifer Scalici, MD         
United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Marquis Simms    410-955-8849    msimms10@jhmi.edu   
Contact: Amy Deery, RN    410-502-0669    ahorne1@jhmi.edu   
Principal Investigator: Deborah Armstrong, MD         
United States, Missouri
Washington University, School of Medicine Recruiting
Saint Louis, Missouri, United States, 63108
Contact: Jehan Ganachaud, M.Sc.    314-747-9202    ganachaud.j@wustl.edu   
Contact: Dave Schwab       dschwab@wustl.edu   
Principal Investigator: Julie Schwarz, MD         
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Heather Neagle, RN, BSN    980-442-2303    Heather.Neagle@Carolinashealthcare.org   
Contact: Melissa Parker       Melissa.M.Parker@atriumhealth.org   
Principal Investigator: Erin Crane, MD         
United States, Oklahoma
University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Braden Curry    405-271-8777    braden-curry@ouhsc.edu   
Contact: HeeSun Kim-Suh       HeeSun-Kim@ouhsc.edu   
Principal Investigator: Katherine Moxley, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Sheena Clift    434-924-2745    SHC2WN@hscmail.mcc.virginia.edu   
Principal Investigator: Linda Duska, MD         
INOVA Fairfax Hospital Recruiting
Falls Church, Virginia, United States, 22042
Contact: Shelby Dukes    703-970-6554    Shelby.Dukes@inova.org   
Contact: Emily Vatannia    571.472.0623    Emily.Vatannia@inova.org   
Principal Investigator: Chad Hamilton         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Pam Loyall    804-628-2667    ployall@vcu.edu   
Contact: Nichole Calandrinno    804-628-2334    calandrinn@vcu.edu   
Principal Investigator: Emma Fields, MD         
Sponsors and Collaborators
Linda R Duska
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Linda Duska, MD University of Virginia
More Information
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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 ( Other Grant/Funding Number: Merck Sharp & Dohme Corp. )
First Posted: December 18, 2015    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Keywords provided by Linda R Duska, University of Virginia:
advanced
cervical cancer
pembrolizumab
chemoradiation
immunotherapy
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
 Uterine Cervical Diseases
Uterine Diseases
Cisplatin
Pembrolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological