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

Conditions

• 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

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Brachytherapy — RADIATION
  Undergo brachytherapy
• Carboplatin — DRUG
  Given IV
• Chest Radiography — PROCEDURE
  Undergo chest x-ray
• Cisplatin — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT scan
• External Beam Radiation Therapy — RADIATION
  Undergo EBRT
• Intensity-Modulated Radiation Therapy — RADIATION
  Undergo IMRT
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Paclitaxel — DRUG
  Given IV
• Pembrolizumab — BIOLOGICAL
  Given IV
• Positron Emission Tomography — PROCEDURE
  Undergo PET scan

Study Details

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.

Key Dates

Start date

Nov 5, 2025

Status verified

May 2026

Primary completion

Dec 31, 2030

Completion

Dec 31, 2030

Study Design

Enrollment

336 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.

Primary Outcome Measure

Progression free survival (PFS) [ Time Frame: From randomization to time of progression or death from any cause, whichever occurs first, or date of last contact if neither progression nor death has occurred, up to 7 years ]

Locations (260)

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