Étude IMagyn050 - Cancer Ovaire

Study description / Fiche descriptive de l'étude

Ovarian study / Étude ovaire

IMagyn050

Study Title / Titre de l'étude

IMagyn050 : A phase III, multicenter, randomized, study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with Newly-diagnosed stage iii or stage iv ovarian, fallopian tube, or primary peritoneal cancer

Current status of the study / Statut

The recruitment period is closed. 

Sponsor / Promoteur

ARCAGY - GINECO

Goal / But

This study will evaluate the efficacy, safety, and pharmacokinetics of atezolizumab administered with paclitaxel + carboplatin + bevacizumab compared with placebo + paclitaxel + carboplatin + bevacizumab in patients with newly-diagnosed, untreated ovarian, fallopian tube, and/or primary peritoneal cancer. Specific objectives and corresponding endpoints for the study are outlined below.

Phase

Phase III

Target Population / Type de patiente

Patients must meet the following criteria for study entry:

• Signed Informed Consent Form (ICF)
• Age ≥ 18 years
• Able to comply with the study protocol, in the investigator’s judgment
• Receive a histologic diagnosis of epithelial ovarian cancer, peritoneal primary carcinoma, or fallopian tube cancer
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2
• Life expectancy > 12 weeks
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization
• For patients who receive therapeutic anticoagulation: stable anticoagulant regimen
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 5 months after administration of the last dose of atezolizumab and 6 months after the last dose of bevacizumab, paclitaxel, or carboplatin, whichever is later
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, that include the completion of patient-reported outcomes questionnaires
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen (either archival specimen or fresh pretreatment tissue) in paraffin blocks (preferred) or at least 20 unstained slides.
• For enrollment into the China extension phase, residence in the People’s Republic of China

Number of patients recruited for this study / Nombre de patientes recrutées

1301 patients have been randomized.

Primary endpoint / Critère principal d’évaluation

Primary Analysis

The primary analysis populations for efficacy are the ITT population, defined as all patients randomized in the study and the PD-L1-positive subgroup, defined as the patients in the ITT population whose PD-L1 status is IC1/2/3 at the time of randomization. Patients will be grouped in accordance with the treatment assigned at randomization.

The primary analysis population for safety is the Safety Population, defined as all randomized patients who receive at least one dose of the study medication. Patients will be grouped in accordance with the treatment they actually receive, and all patients who received any dose of atezolizumab will be included in the atezolizumab treatment arm for analysis.

Determination of Sample Size

There are two co-primary efficacy endpoints: investigator-assessed progression-free survival (PFS) and overall survival (OS). The overall Type I error rate will be controlled at a two-sided level of 0.05 to test PFS and OS in the PD-L1-positive subgroup and the ITT population. PFS in both the ITT and PD-L1-positive subgroup will be tested in parallel at the same significance level of 0.002 (two-sided). To test OS in both these specified populations, a hierarchical testing approach will be applied. The alpha allocated to OS will be used first to test OS in the PD-L1-positive subgroup. If the significance is reached, the same alpha as used for the PD -L1-positive subgroup OS testing will be passed to OS in the ITT. Note that the OS testing sequence of the populations may be inverted. The OS test in the PD-L1-positive subgroup is initially assigned with an alpha level of 0.046 and the actual alpha level will be determined by the results of the PFS tests. If the PFS test in either the ITT or PD-L1-positive population reaches significance, its assigned alpha of 0.002 will be additively passed to OS.

The sample size of the study is determined by the number of patient deaths required to demonstrate efficacy in terms of OS in the PD-L1-positive subgroup and the ITT population. To detect an improvement in OS with the use of a log-rank test at a two-sided significance level of 0.046, approximately 311 deaths in the PD-L1-positive subgroup will be required to achieve 81% power with a target HR of 0.72, and approximately 534 deaths in the ITT population to achieve 80% power with a target HR of 0.78.