External Beam Radiation Therapy and Brachytherapy With Chemotherapy and Immunotherapy for the Treatment of Stage IVB Cervical Cancer
brief summary
This phase I/II trial tests the safety and effectiveness of receiving external beam radiation therapy (EBRT) and brachytherapy along with chemotherapy, consisting of cisplatin and paclitaxel, and immunotherapy, consisting of bevacizumab and pembrolizumab, for the treatment of patients with stage IVB cervical cancer. EBRT is type of radiation therapy that uses a machine to aim high-energy rays at the cancer from outside of the body. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving EBRT and brachytherapy along with chemotherapy and immunotherapy may be a safe and effective way to treat patients with stage IVB cervical cancer.
detailed description
PRIMARY OBJECTIVE:
I. To demonstrate that radiotherapy can be safely integrated into chemotherapy and pembrolizumab with bevacizumab in newly diagnosed stage IVB cervical cancer to improve outcomes.
SECONDARY OBJECTIVE:
I. To demonstrate improvements with overall response rate, overall survival (OS), and duration of response with the addition of radiation therapy to standard of care in stage IVB cervical cancer.
EXPLORATORY OBJECTIVES:
I. To demonstrate improved quality of life and disease-related toxicity with the addition of radiation therapy to standard of care chemotherapy in stage IVB cervical cancer.
II. To explore the association of known risk factors (age, race/ethnicity, smoking status, baseline quality of life, combined positive score \[CPS\] score 1-10 versus \> 10, and performance status with the change in QOL, treatment outcomes, and toxicities.
III. To explore circulating tumor deoxyribonucleic acid (ctDNA) as a biomarker to monitor the response to upfront chemotherapy-immunotherapy and subsequent radiation.
IV. To use T cell receptor repertoire sequencing (TCRseq) to define T cell clones present in the tumor and to establish their concordance with peripheral blood T cell clones at baseline and in response to therapy.
OUTLINE:
PART 1: Patients receive cisplatin intravenously (IV), paclitaxel IV, pembrolizumab IV over 30 minutes, and bevacizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive no treatment for 3 weeks.
PART 2: Patients undergo EBRT for 25 treatments delivered over 5 weeks, and brachytherapy over 3-5 treatments. Patients also receive pembrolizumab IV over 30 minutes and bevacizumab IV on day 1 of each cycle. Cycles for immunotherapy repeat every 21 days for a total of 2 years in the absence of disease progression or unacceptable toxicity. Participants who complete study intervention after 2 years of pembrolizumab are eligible for up to 1 year of additional pembrolizumab (second course) upon experiencing disease progression.
official title
A Prospective Cohort Study of Integrating Radiotherapy Into Chemotherapy With Pembrolizumab and Bevacizumab in Newly Diagnosed Stage IVB Cervical Cancer