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
Location: See all (41) locations...
Intervention Type: Procedure, Drug, Radiation, Biological
Study Type: Interventional
Study Phase: Phase 3
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.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• 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)

⁃ 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)

Locations
United States
Alabama
University of Alabama at Birmingham Cancer Center
RECRUITING
Birmingham
Delaware
Helen F Graham Cancer Center
RECRUITING
Newark
Medical Oncology Hematology Consultants PA
RECRUITING
Newark
Florida
Broward Health Medical Center
RECRUITING
Fort Lauderdale
Idaho
Kootenai Health - Coeur d'Alene
SUSPENDED
Coeur D'alene
Kootenai Clinic Cancer Services - Post Falls
SUSPENDED
Post Falls
Illinois
Northwestern University
RECRUITING
Chicago
Cancer Care Specialists of Illinois - Decatur
RECRUITING
Decatur
Decatur Memorial Hospital
RECRUITING
Decatur
Crossroads Cancer Center
SUSPENDED
Effingham
Southern Illinois University School of Medicine
RECRUITING
Springfield
Springfield Clinic
RECRUITING
Springfield
Springfield Memorial Hospital
RECRUITING
Springfield
Maine
MaineHealth Coastal Cancer Treatment Center
RECRUITING
Bath
MaineHealth Maine Medical Center - Portland
RECRUITING
Portland
MaineHealth Cancer Care Center of York County
RECRUITING
Sanford
MaineHealth Maine Medical Center- Scarborough
RECRUITING
Scarborough
Michigan
Trinity Health Saint Joseph Mercy Oakland Hospital
SUSPENDED
Pontiac
Missouri
Freeman Health System
RECRUITING
Joplin
Mercy Hospital Springfield
RECRUITING
Springfield
Mercy Hospital Saint Louis
RECRUITING
St Louis
Montana
Community Medical Center
SUSPENDED
Missoula
Nebraska
Nebraska Methodist Hospital
SUSPENDED
Omaha
New Jersey
Memorial Sloan Kettering Basking Ridge
RECRUITING
Basking Ridge
Memorial Sloan Kettering Monmouth
RECRUITING
Middletown
Memorial Sloan Kettering Bergen
RECRUITING
Montvale
New York
Roswell Park Cancer Institute
RECRUITING
Buffalo
Memorial Sloan Kettering Commack
RECRUITING
Commack
Memorial Sloan Kettering Westchester
RECRUITING
Harrison
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Memorial Sloan Kettering Nassau
RECRUITING
Uniondale
Ohio
University of Cincinnati Cancer Center-UC Medical Center
RECRUITING
Cincinnati
ProMedica Flower Hospital
RECRUITING
Sylvania
University of Cincinnati Cancer Center-West Chester
RECRUITING
West Chester
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Pennsylvania
Lehigh Valley Hospital-Cedar Crest
RECRUITING
Allentown
Lehigh Valley Hospital - Muhlenberg
RECRUITING
Bethlehem
Pocono Medical Center
RECRUITING
East Stroudsburg
Thomas Jefferson University Hospital
RECRUITING
Philadelphia
Asplundh Cancer Pavilion
RECRUITING
Willow Grove
Rhode Island
Women and Infants Hospital
SUSPENDED
Providence
Time Frame
Start Date: 2025-11-05
Estimated Completion Date: 2030-12-31
Participants
Target number of participants: 336
Treatments
Active_comparator: 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.
Experimental: 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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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