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

Launched by NATIONAL CANCER INSTITUTE (NCI) · Jul 11, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new approach to treating women with advanced cervical cancer that has spread to nearby tissues or lymph nodes. The study is comparing two treatment plans: one starts with a combination of chemotherapy drugs (carboplatin and paclitaxel) plus an immunotherapy drug called pembrolizumab before moving on to the usual chemotherapy and radiation treatment with pembrolizumab; the other plan follows the standard treatment of chemotherapy and radiation with pembrolizumab from the start. The goal is to see if adding this initial chemotherapy and immunotherapy can improve outcomes for women with high-risk cervical cancer.

Women who may be eligible for this trial are those newly diagnosed with certain types of cervical cancer (squamous cell, adenocarcinoma, or adenosquamous carcinoma) at specific advanced stages, where the cancer has grown into nearby tissues or lymph nodes but not spread further. Participants should be adults in good enough health to tolerate treatment, not pregnant or breastfeeding, and without serious infections or immune system problems. If they join, patients will receive close monitoring and treatment as outlined in the study, including various scans and blood tests to track how well the cancer responds. This trial is not yet open for enrollment but aims to find better ways to treat advanced cervical cancer with the help of new chemotherapy and immunotherapy combinations.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Patients must have pathologically confirmed newly diagnosed cervical cancer. Eligible pathologic types: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma
• * 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)