Description:
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.
Title
- Brief Title: Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer
- Official Title: A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
Clinical Trial IDs
- ORG STUDY ID:
18472
- SECONDARY ID:
UVA-LACC-PD201
- NCT ID:
NCT02635360
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Pembrolizumab | Keytruda, MK-3475 | Concurrent to chemoradiation |
| Cisplatin | chemotherapy | Concurrent to chemoradiation |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | |
| 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. | |
Eligibility 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Change in immunologic markers following combination of study drug with chemoradiation |
| Time Frame: | At 6 weeks of chemoradiation and 12 weeks post-chemoradiation |
| Safety Issue: | |
| Description: | Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared. |
Secondary Outcome Measures
| Measure: | Metabolic Response Rate on PET/CT imaging |
| Time Frame: | 12 weeks after chemotherapy |
| Safety Issue: | |
| Description: | |
| Measure: | Incidence of distant metastases |
| Time Frame: | From start of treatment until up to 5 years following end of treatment |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival |
| Time Frame: | From start of treatment until up to 5 years following end of treatment |
| Safety Issue: | |
| Description: | |
| Measure: | Overall Survival |
| Time Frame: | From start of treatment until up to 5 years following end of treatment |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Linda R Duska |
Trial Keywords
- advanced
- cervical cancer
- pembrolizumab
- chemoradiation
- immunotherapy
Last Updated
April 28, 2021
