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
NCT ID: NCT07061977
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE3
336 participants
INTERVENTIONAL
2025-11-05
2030-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm 1 (Standard care)
CHEMORADIATION: Patients receive cisplatin IV QW for 5 weeks and pembrolizumab IV over 30 minutes Q3W for 5 doses. Patients also undergo radiation therapy with EBRT or IMRT 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 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.
Biospecimen Collection
Undergo blood sample collection
Brachytherapy
Undergo brachytherapy
Chest Radiography
Undergo chest x-ray
Cisplatin
Given IV
Computed Tomography
Undergo CT scan
External Beam Radiation Therapy
Undergo EBRT
Intensity-Modulated Radiation Therapy
Undergo IMRT
Magnetic Resonance Imaging
Undergo MRI
Pembrolizumab
Given IV
Positron Emission Tomography
Undergo PET scan
Arm 2 (induction and standard care)
INDUCTION: Patients receive carboplatin IV and paclitaxel IV QW on weeks 1-3 and pembrolizumab IV over 30 minutes Q3W on week 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 with EBRT or IMRT 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.
Biospecimen Collection
Undergo blood sample collection
Brachytherapy
Undergo brachytherapy
Carboplatin
Given IV
Chest Radiography
Undergo chest x-ray
Cisplatin
Given IV
Computed Tomography
Undergo CT scan
External Beam Radiation Therapy
Undergo EBRT
Intensity-Modulated Radiation Therapy
Undergo IMRT
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Pembrolizumab
Given IV
Positron Emission Tomography
Undergo PET scan
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Biospecimen Collection
Undergo blood sample collection
Brachytherapy
Undergo brachytherapy
Carboplatin
Given IV
Chest Radiography
Undergo chest x-ray
Cisplatin
Given IV
Computed Tomography
Undergo CT scan
External Beam Radiation Therapy
Undergo EBRT
Intensity-Modulated Radiation Therapy
Undergo IMRT
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Pembrolizumab
Given IV
Positron Emission Tomography
Undergo PET scan
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients must have locally advanced cervical cancer (LACC) with T3 or T4 disease with or without lymph node involvement:
* IIIA (T3aN0M0)
* IIIB (T3bN0M0)
* IIIC1(T3aN1M0, T3bN1M0)
* IIIC2 (T3aN2M0, T3bN2M0)
* IVA (T4aN0M0, T4aN1M0, T4aN2M0) No prior hysterectomy defined as removal of the entire uterus.
* NOTE: prior partial/subtotal hysterectomy for reasons other than cervical cancer are eligible to participate in the study. No plan to perform a hysterectomy as part of initial cervical cancer therapy.
No paraaortic lymph node (PALN) metastases above the T12/L1 interspace.
* Note: Nodal status can be confirmed by imaging (CT, MRI, or PET/CT), fine needle aspirate/core biopsy, extra peritoneal biopsy, laparoscopic biopsy, or lymphadenectomy.
Radiologic definition of lymph node staging:
* N1:
* One or more pelvic lymph nodes with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
* One or more pelvic lymph nodes with short axis diameter of ≥ 10 mm and standardized uptake value maximum (SUVmax) ≥ 2.5 by fludeoxyglucose (FDG)-PET
* N2:
* One or more para-aortic lymph node with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
* One or more para-aortic lymph node with short axis diameter of ≥ 10 mm and SUVmax ≥ 2.5 by FDG-PET
* No prior definitive surgical, radiation, or systemic therapy for cervical cancer
* No prior immunotherapy
* No prior pelvic radiation therapy for any disease
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobulin \[Hgb\] ≥ 8 g/dl is acceptable)
* Creatinine clearance (CrCL) of ≥ 50 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parenteral antibiotics
* No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed
* No diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior registration
* No active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
* No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)
18 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Jyoti S Mayadev
Role: PRINCIPAL_INVESTIGATOR
NRG Oncology
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Crossroads Cancer Center
Effingham, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Springfield Clinic
Springfield, Illinois, United States
Springfield Memorial Hospital
Springfield, Illinois, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, United States
Mercy Hospital Springfield
Springfield, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Community Medical Center
Missoula, Montana, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Memorial Sloan Kettering Westchester
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, United States
ProMedica Flower Hospital
Sylvania, Ohio, United States
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, United States
Pocono Medical Center
East Stroudsburg, Pennsylvania, United States
Women and Infants Hospital
Providence, Rhode Island, United States
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2025-04695
Identifier Type: REGISTRY
Identifier Source: secondary_id
NRG-GY037
Identifier Type: OTHER
Identifier Source: secondary_id
NRG-GY037
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2025-04695
Identifier Type: -
Identifier Source: org_study_id