Trial Assessing the Inhibitor of Programmed Cell Death Ligand 1 (PD-L1) Immune Checkpoint Atezolizumab

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT03612791
Phase
PHASE2
Status
Completed

Conditions

  • Locally Advanced Cervical Cancer

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab — DRUG
    atezolizumab administered IV 1200 mg Q3W, starting one week before EBRT (Week -1) and continued as an adjuvant for a total maximum of 20 cycles.
  • Radiotherapy — RADIATION
    * Pelvic +/- para-aortic EBRT (IMRT): 45 Gy in 25 fractions over 5 weeks (Weeks 1-5, with simultaneously integrated boosts to macroscopically involved lymph nodes, if any, in order to deliver a total dose of 60 Gy to macroscopic lymph nodes (including the dose delivered by brachytherapy). * Uterovaginal brachytherapy (Week 7; maximum interval between EBRT and brachytherapy: 14 days). If appropriate and feasible, dose escalation will be assumed, particularly for advanced disease, with the objective to deliver a total dose of 85 Gy (equivalent dose in 2-Gy fractions with α/β=10 Gy) to 80% of the High Risk-Clinical Target Volume (HR-CTV), including 45 Gy through EBRT. The total dose might be lower in case of close proximity to organs at risk (OARs). * Total duration of RT (including brachytherapy) should be ≤ 55 days.
  • Cisplatin — DRUG
    * Cisplatin infused 40 mg/m2 (maximum 70 mg) weekly IV during EBRT (Weeks 1-5). * Not administered: during the interval between EBRT and brachytherapy, or during brachytherapy, or if radiotherapy is interrupted.

Study Details

The primary objective of this randomized phase II trial is to evaluate the clinical benefits of the addition of atezolizumab to standard chemoradiotherapy (CRT) (first given concurrently with CRT, then continued as adjuvant treatment), compared with CRT alone, on investigator-assessed progression-free survival (PFS), as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Key Dates

Start date
Aug 13, 2018
Status verified
Mar 2026
Primary completion
Feb 26, 2024
Completion
May 13, 2025

Study Design

Enrollment
189 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Standard Treatment Arm
    Radiotherapy (RT): * Pelvic +/- para-aortic EBRT (IMRT): 45 Gy in 25 fractions over 5 weeks (Weeks 1-5, with simultaneously integrated boosts to macroscopically involved lymph nodes, if any, in order to deliver a total dose of 60 Gy to macroscopic lymph nodes (including the dose delivered by brachytherapy). * Uterovaginal brachytherapy (Week 7; maximum interval between EBRT and brachytherapy: 14 days). If appropriate and feasible, dose escalation will be assumed, particularly for advanced disease, with the objective to deliver a minimal total dose of 85 Gy (equivalent dose in 2-Gy fractions with α/β=10 Gy) to 80% of the High Risk-Clinical Target Volume (HR-CTV), including 45 Gy through EBRT. The total dose might be lower in case of close proximity to organs at risk (OARs). * Total duration of RT (including brachytherapy) should be ≤ 55 days. Chemotherapy: \- Cisplatin infused 40 mg/m2 (maximum 70 mg) weekly IV during EBRT (Weeks 1-5).
  • Experimental: Experimental Treatment Arm
    * Same treatment as described above (CRT, followed by uterovaginal brachytherapy), plus * atezolizumab administered IV 1200 mg Q3W, starting on the same week as EBRT (Week 1) and continued as an adjuvant for a total maximum of 20 cycles (approximately 14 months total of treatment).

Primary Outcome Measure

Progression Free Survival (PFS) [ Time Frame: from randomization to the first documented occurrence of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurs first, up to 24 months ]

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