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NCT07061977 | RECRUITING | Locally Advanced Cervical Adenocarcinoma

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
Sponsor:

National Cancer Institute (NCI)

Brief 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.

Condition or disease

Locally Advanced Cervical Adenocarcinoma

Locally Advanced Cervical Adenosquamous Carcinoma

Locally Advanced Cervical Squamous Cell Carcinoma

Stage IIIA Cervical Cancer FIGO 2018

Stage IIIB Cervical Cancer FIGO 2018

Stage IIIC1 Cervical Cancer FIGO 2018

Stage IIIC2 Cervical Cancer FIGO 2018

Stage IVA Cervical Cancer FIGO 2018

Intervention/treatment

Biospecimen Collection

Brachytherapy

Carboplatin

Chest Radiography

Cisplatin

Computed Tomography

External Beam Radiation Therapy

Intensity-Modulated Radiation Therapy

Magnetic Resonance Imaging

Paclitaxel

Pembrolizumab

Positron Emission Tomography

Phase

PHASE3

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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 336 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : 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
Actual Study Start Date : 2026-06-26
Estimated Primary Completion Date : 2030-12-31
Estimated Study Completion Date : 2030-12-31

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: FEMALE
Accepts Healthy Volunteers:
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)
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

Location Details

NCT07061977

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, Idaho

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States, 83814

RECRUITING

United States, Idaho

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States, 83854

RECRUITING

United States, Illinois

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States, 62526

RECRUITING

United States, Illinois

Decatur Memorial Hospital

Decatur, Illinois, United States, 62526

RECRUITING

United States, Illinois

Crossroads Cancer Center

Effingham, Illinois, United States, 62401

RECRUITING

United States, Illinois

Southern Illinois University School of Medicine

Springfield, Illinois, United States, 62702

RECRUITING

United States, road cancer

Trinity Health Saint Joseph Mercy Oakland Hospital

Pontiac, road cancer, United States, 48341

RECRUITING

United States, Missouri

Mercy Hospital Springfield

Springfield, Missouri, United States, 65804

RECRUITING

United States, Missouri

Mercy Hospital Saint Louis

St Louis, Missouri, United States, 63141

RECRUITING

United States, Montana

Community Medical Center

Missoula, Montana, United States, 59804

RECRUITING

United States, Nebraska

Nebraska Methodist Hospital

Omaha, Nebraska, United States, 68114

RECRUITING

United States, New Jersey

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States, 07920

RECRUITING

United States, New Jersey

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States, 07748

RECRUITING

United States, New Jersey

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States, 07645

RECRUITING

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

RECRUITING

United States, New York

Memorial Sloan Kettering Commack

Commack, New York, United States, 11725

RECRUITING

United States, New York

Memorial Sloan Kettering Westchester

Harrison, New York, United States, 10604

RECRUITING

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

RECRUITING

United States, New York

Memorial Sloan Kettering Nassau

Uniondale, New York, United States, 11553

RECRUITING

United States, Ohio

ProMedica Flower Hospital

Sylvania, Ohio, United States, 43560