A Phase III Study Of Induction Pembrolizumab And Chemotherapy Followed By Chemoradiation And Pembrolizumab Vs Chemoradiation And Pembrolizumab Both Followed By Pembrolizumab For High Risk Locally Advanced Cervical Cancer.
Primary Objective:
To determine whether induction IO and chemotherapy prior to CCRT+IO improves progression-free survival (PFS) compared to CCRT+IO alone.
Secondary Objectives:
1. To assess whether induction IO and chemotherapy prior to CCRT+IO improves the overall survival (OS) compared to CCRT+IO alone.
2. 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 CTCAE v5.0.
3. 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.
4. To assess the association between allostatic load and PFS/OS.
5. To assess the predictive value of the integrated biomarker: PD-L1 expression at baseline for progression free survival.
6. To assess the prognostic and predictive value of the integrated biomarker: ctDNA at
baseline and at 3 months post RT for progression free survival.
7. To explore radiotherapy quality pretreatment scores conducted by expert review with
assistance from AI models and correlation with outcomes.
CISPLATIN
PACLITAXEL
Pembrolizumab (MK-3475)
- RWJBarnabas Health
- Jersey City Medical Center, Jersey City
- Rutgers University
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)
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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