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Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

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ClinicalTrials.gov Identifier: NCT02635360
Recruitment Status : Active, not recruiting
First Posted : December 18, 2015
Last Update Posted : April 28, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Linda R Duska, University of Virginia

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.

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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
Actual Primary Completion Date : January 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

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




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 ]


Information from the National Library of Medicine

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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.

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


Locations
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United States, Alabama
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University, School of Medicine
Saint Louis, Missouri, United States, 63108
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
INOVA Fairfax Hospital
Falls Church, Virginia, United States, 22042
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Linda R Duska
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Linda Duska, MD University of Virginia
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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: April 28, 2021
Last Verified: April 2021
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
Pembrolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological