Clinical trial NCT02635360: Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer
Official title: A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: advanced
cervical cancer
pembrolizumab
chemoradiation
immunotherapy
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-12-18
Enrollment: 88
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Change in immunologic markers following combination of study drug with chemoradiation
timeFrame: At 6 weeks of chemoradiation and 12 weeks post-chemoradiation
measure: Incidence of dose limiting toxicities
timeFrame: From start of treatment until 12 weeks post-chemoradiation
Secondary outcomes:
measure: Metabolic Response Rate on PET/CT imaging
timeFrame: 12 weeks after chemotherapy
measure: Incidence of distant metastases
timeFrame: From start of treatment until up to 5 years following end of treatment
measure: Progression Free Survival
timeFrame: From start of treatment until up to 5 years following end of treatment
measure: Overall Survival
timeFrame: From start of treatment until up to 5 years following end of treatment
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Saint Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: INOVA Fairfax Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: University of Virginia
name: Linda Duska, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.