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.
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
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
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Overview
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Study details
- 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. - 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
- With paraaortic lymph node (PALN) metastases above the T12/L1 interspace.
- Radiologic definition of lymph node staging N2: prior immunotherapy
- Radiologic definition of lymph node staging N2: prior definitive surgical, radiation, or systemic therapy for cervical cancer
1) 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.
2) 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.