Cervical CancerPhase 2NCT02635360
Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer
A Phase 2 study testing Pembrolizumab, Brachytherapy and Cisplatin in people with Cervical Cancer, run by Linda R Duska at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Cancer
- What is being tested?
- Pembrolizumab, Brachytherapy and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 8 sitesUnited States
- Study dates
- 9 Feb 2017to 14 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed cervical cancer.
- Must have adequate organ function.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins
Baltimore, Maryland, 21287
Levine Cancer Institute
Charlotte, North Carolina, 28204
University of Virginia
Charlottesville, Virginia, 22908
INOVA Fairfax Hospital
Falls Church, Virginia, 22042
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, 36604
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Virginia Commonwealth University
Richmond, Virginia, 23298
Washington University, School of Medicine
St Louis, Missouri, 63108
About this study
Official title: A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
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.
Read the 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.
- Conditions
- Cervical Cancer
- Being tested
- Pembrolizumab, Brachytherapy, Cisplatin
- Keywords
- advanced, cervical cancer, pembrolizumab, chemoradiation, immunotherapy
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, MK-3475
200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months.
BrachytherapyRadiation
Also called chemoradiation
Radiation is done for standard clinical care purposes.
CisplatinDrug
Also called chemotherapy
40 mg of chemotherapy drug will be given weekly for 5-6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Following chemoradiation | Experimental | 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. Receives: Drug: Pembrolizumab; Radiation: Brachytherapy; Drug: Cisplatin |
| Concurrent to chemoradiation | Experimental | 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. Receives: Drug: Pembrolizumab; Radiation: Brachytherapy; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Immunologic Markers Following Combination of Study Drug With Chemoradiation
Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared, analyzed and enumerated using QuPath software to provide a cell #/mm2 (not per high power field) and the ratio of CD8+ cells:FoxP3+ cells/mm2 was calculated.
Measured: 12 weeks post-chemoradiation
Number of Participants With Dose Limiting Toxicities
To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer
Measured: From start of treatment until 12 weeks post-chemoradiation
Secondary outcomes (4)
Metabolic Response Rate on PET/CT Imaging
To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT
Measured: 12 weeks after chemotherapy
Incidence of Distant Metastases
To estimate the rates of distant metastasis as the first site of recurrent for patients
Measured: From start of treatment until up to 5 years following end of treatment
Progression Free Survival
To estimate the progression free survival (PFS) in subjects with locally advanced cervical cancer treatment with sequential and concurrent administration of pembrolizumab in relation to CRT
Measured: From start of treatment until up to 5 years following end of treatment
Overall Survival
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
Measured: From start of treatment until up to 5 years following end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2015 (estimated)
- Study start9 Feb 2017
- Primary completion1 Jan 2021
- Study completion14 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Linda R Duska
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Linda R Duska, University of Virginia
- Investigators
- Linda Duska, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02635360
- Sponsor's protocol ID
- 18472
- Other IDs
- UVA-LACC-PD201
- Status last verified
- Jun 2025
- First submitted
- 4 Dec 2015
- Last updated
- 3 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33581976
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
- ClinicalTrials.gov ID
- NCT02635360
- Acronym / sponsor ID
- 18472
- Conditions
- Cervical Cancer
- Keywords
- advanced, cervical cancer, pembrolizumab, chemoradiation, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Linda R DuskaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 9 Feb 2017 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 14 Dec 2022 (actual)
- First posted
- 18 Dec 2015 (estimated)
- Results
- Posted 3 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Following chemoradiation | Experimental | Drug: Pembrolizumab, Radiation: Brachytherapy, Drug: CisplatinSubjects 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. |
| Concurrent to chemoradiation | Experimental | Drug: Pembrolizumab, Radiation: Brachytherapy, Drug: CisplatinSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Confirmed cervical cancer.
- Must have adequate organ function.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. | Drug | Concurrent to chemoradiation, Following chemoradiation |
| BrachytherapyAlso: chemoradiationRadiation is done for standard clinical care purposes. | Radiation | Concurrent to chemoradiation, Following chemoradiation |
| CisplatinAlso: chemotherapy40 mg of chemotherapy drug will be given weekly for 5-6 weeks. | Drug | Concurrent to chemoradiation, Following chemoradiation |
Primary outcome
Change in Immunologic Markers Following Combination of Study Drug With Chemoradiation
Time frame: 12 weeks post-chemoradiation
Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared, analyzed and enumerated using QuPath software to provide a cell #/mm2 (not per high power field) and the ratio of CD8+ cells:FoxP3+ cells/mm2 was calculated.
Number of Participants With Dose Limiting Toxicities
Time frame: From start of treatment until 12 weeks post-chemoradiation
To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer
4 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33581976Lin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda Duska, MD principal investigator
University of Virginia
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Brachytherapy and Cisplatin in people with Cervical Cancer, run by Linda R Duska at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Immunologic Markers Following Combination of Study Drug With Chemoradiation (time frame: 12 weeks post-chemoradiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02635360, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.