Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

NCT ID: NCT02635360

Last Updated: 2025-07-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

94 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-09

Study Completion Date

2022-12-14

Brief Summary

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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

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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.

Conditions

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Cervical Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months.

Brachytherapy

Intervention Type RADIATION

Radiation is done for standard clinical care purposes.

Cisplatin

Intervention Type DRUG

40 mg of chemotherapy drug will be given weekly for 5-6 weeks.

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months.

Brachytherapy

Intervention Type RADIATION

Radiation is done for standard clinical care purposes.

Cisplatin

Intervention Type DRUG

40 mg of chemotherapy drug will be given weekly for 5-6 weeks.

Interventions

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Pembrolizumab

200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months.

Intervention Type DRUG

Brachytherapy

Radiation is done for standard clinical care purposes.

Intervention Type RADIATION

Cisplatin

40 mg of chemotherapy drug will be given weekly for 5-6 weeks.

Intervention Type DRUG

Other Intervention Names

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Keytruda MK-3475 chemoradiation chemotherapy

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Linda R Duska

OTHER

Sponsor Role lead

Responsible Party

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Linda R Duska

Associate Professor, Division of Gynecology Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Linda Duska, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

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University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, United States

Site Status

Johns Hopkins

Baltimore, Maryland, United States

Site Status

Washington University, School of Medicine

St Louis, Missouri, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

INOVA Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Lin AJ, Dehdashti F, Massad LS, Thaker PH, Powell MA, Mutch DG, Schwarz JK, Markovina S, Siegel BA, Grigsby PW. Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response. Clin Oncol (R Coll Radiol). 2021 May;33(5):300-306. doi: 10.1016/j.clon.2021.01.010. Epub 2021 Feb 11.

Reference Type DERIVED
PMID: 33581976 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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UVA-LACC-PD201

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

18472

Identifier Type: -

Identifier Source: org_study_id

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