Trials / Recruiting

RecruitingNCT07061977

Induction Pembrolizumab and Chemotherapy Followed by Pembrolizumab Before Chemoradiation and Pembrolizumab Maintenance Compared to Standard Chemoradiation With Pembrolizumab Followed by Pembrolizumab Maintenance in High-Risk Cervical Cancer

NRG-GY037: A Phase III Study of Induction Pembrolizumab and Chemotherapy Followed by Chemoradiation and Pembrolizumab Versus Chemoradiation and Pembrolizumab Both Followed by Pembrolizumab for High Risk Locally Advanced Cervical Cancer

Status: Recruiting
Phase: Phase 3
Study type: Interventional
Enrollment: 336 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase III trial compares the addition of induction chemotherapy, with carboplatin, paclitaxel and pembrolizumab, to chemotherapy and radiation, with cisplatin and pembrolizumab followed by pembrolizumab maintenance for the treatment of patients with cervical cancer that has spread to nearby tissue or lymph nodes (locally advanced). Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Adding induction chemotherapy to the usual treatment of chemotherapy and radiation followed by maintenance may be more effective in treating patients with high risk, locally advanced cervical cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine whether induction immunotherapy (IO) and chemotherapy prior to concurrent chemoradiation therapy (CCRT) + IO improves progression-free survival (PFS) compared to CCRT+IO alone. SECONDARY OBJECTIVES: I. To assess whether induction IO and chemotherapy prior to CCRT+IO improves the overall survival (OS) compared to CCRT+IO alone. II. To determine the nature and degree of toxicity of induction IO and chemotherapy prior to CCRT + IO as compared to concurrent CCRT+IO as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. III. To determine the impact on CCRT start, CCRT completion time, and number of cycles of cisplatin administered; with induction IO and chemotherapy prior to CCRT+IO arm as compared to CCRT+IO. IV. To assess the association between allostatic load and PFS/OS. V. To assess the predictive value of the integrated biomarker: PD-L1 expression at baseline for progression free survival. VI. To assess the prognostic and predictive value of the integrated biomarker: circulating tumor deoxyribonucleic acid (ctDNA) at baseline and at 3 months post radiation therapy (RT) for progression free survival. VII. To explore radiotherapy quality pretreatment scores conducted by expert review with assistance from artificial intelligence (AI) models and correlation with outcomes. EXPLORATORY OBJECTIVES: I. To assess the evolution of T cell receptor (TCR) repertoire on treatment and its correlation with clinical outcomes. II. To identify pre-treatment tumor microenvironment biomarkers predictive of outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: CHEMORADIATION: Patients receive cisplatin intravenously (IV) once weekly (QW) for 5 weeks and pembrolizumab IV over 30 minutes every 3 weeks (Q3W) for 5 doses. Patients also undergo radiation therapy once daily 5 days per week for 25-29 treatments in weeks 1-5 followed by brachytherapy up to twice per week for 4-5 treatments in weeks 5-7. Treatment is given in the absence of disease progression or unacceptable toxicity MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes every 6 weeks (Q6W) for 15 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET) scan, computed tomography (CT) scan, chest x-ray and/or magnetic resonance imaging (MRI) and blood sample collection throughout the study. ARM 2: INDUCTION: Patients receive carboplatin IV and paclitaxel IV QW on weeks 1-3 and pembrolizumab IV over 30 minutes Q3W on weeks 1 for each cycle. Cycles repeat every 3 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. CHEMORADIATION: Patients receive cisplatin IV QW for 5 weeks and pembrolizumab IV over 30 minutes every Q3W for 5 doses. Patients also undergo radiation therapy once daily 5 days per week for 25-29 treatments in weeks 7-11 followed by brachytherapy up to twice per week for 4-5 treatments in weeks 11-13. Treatment is given in the absence of disease progression or unacceptable toxicity MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes Q6W for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan, CT scan, chest x-ray and/or MRI and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for 3 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
RADIATION	Brachytherapy	Undergo brachytherapy
DRUG	Carboplatin	Given IV
PROCEDURE	Chest Radiography	Undergo chest x-ray
DRUG	Cisplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT scan
RADIATION	External Beam Radiation Therapy	Undergo EBRT
RADIATION	Intensity-Modulated Radiation Therapy	Undergo IMRT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Paclitaxel	Given IV
BIOLOGICAL	Pembrolizumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET scan

Timeline

Start date: 2025-11-05
Primary completion: 2030-12-31
Completion: 2030-12-31
First posted: 2025-07-14
Last updated: 2026-04-17

Locations

201 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT07061977. Inclusion in this directory is not an endorsement.