Pembrolizumab and Chemoradiation Treatment for Advanced Cervical Cancer

Cervical Cancer Clinical Trial

Official title:

A Randomized Phase II Study of Chemoradiation and Pembrolizumab for Locally Advanced Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02635360
• Other study ID #: 18472
• Secondary ID: UVA-LACC-PD201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 2016
• Est. completion date: December 2021

Study information

• Verified date: April 2021
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 88
• Est. completion date: December 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

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

Radiation:
• Brachytherapy
Radiation is done for standard clinical care purposes.

Drug:
• Cisplatin
40 mg of chemotherapy drug will be given weekly for 5-6 weeks.

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	INOVA Fairfax Hospital	Falls Church	Virginia
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University, School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Linda R Duska	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 6 weeks of chemoradiation and 12 weeks post-chemoradiation
Primary	Incidence of dose limiting toxicities		From start of treatment until 12 weeks post-chemoradiation
Secondary	Metabolic Response Rate on PET/CT imaging		12 weeks after chemotherapy
Secondary	Incidence of distant metastases		From start of treatment until up to 5 years following end of treatment
Secondary	Progression Free Survival		From start of treatment until up to 5 years following end of treatment
Secondary	Overall Survival		From start of treatment until up to 5 years following end of treatment