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Étude FIRST - Cancer Ovaire

Étude en cours de recrutement

Fiche descriptive de l'étude

Étude ovaire

FIRST

Title of Study / Titre de l'étude

The FIRST (First line ovarian cancer treatment with Niraparib plus TSR 042) Study: An Adaptive Randomized Phase 3 Comparison of Standard Platinum based Treatment versus Platinum and TSR-042 Followed by Niraparib and TSR-042 Maintenance Therapy in Patients with Epithelial Stage III or IV Cancer of the Ovary, Fallopian Tube, or Peritoneum

Statut

This study being to recruited. / Cette étude est en cours de recrutement.

Name of Sponsor/Company / Promoteur

TESARO, Inc.

Goal / But

Primary Objective

  • To compare the progression-free survival (PFS) of patients with Stage III or IV non-mucinous epithelial ovarian cancer treated with platinum-based therapy and TSR-042 followed by niraparib and TSR-042 maintenance therapy with standard first line platinum-based therapy. The primary PFS analysis will be based upon Investigator assessment per RECIST v1.1. A sensitivity analysis of PFS based upon blinded independent central review committee (BICR) will be conducted as well.

Secondary Objectives

  • Overall survival (OS)
  • Objective response rate (ORR)
  • Duration of response (DOR)
  • Disease Control Rate (DCR)
  • Time to first subsequent therapy (TFST)
  • Time to second subsequent therapy (TSST)
  • Time from treatment randomization to the earliest date of assessment of progression on the next anticancer therapy following study treatment or death by any cause (PFS2)
  • RECIST v. 1.1 or CA-125 progression-free survival
  • Patient-reported outcomes (PROs)
  • Safety and tolerability of all treatments

Exploratory Objectives

  • To retrospectively evaluate biomarkers related to ovarian cancer, PARP inhibition and PD-1 therapy (e.g. DNA repair pathways, immune checkpoint pathway, etc.)
  • To assess population pharmacokinetics (PK) and immunogenicity (TSR-042 only) and measure PK parameters for niraparib and TSR-042

Phase

Phase III

Criteria for Inclusion / Type de patiente

To be considered eligible to participate in this study, all of the following requirements must be met:

  • Patient must be female, ≥18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent.
  • Patient with non-mucinous epithelial ovarian cancer that is Stage III or IV according to the International Federation of Gynecology and Obstetrics (FIGO), JACC or TNM criteria. Patient with clear cell ovarian cancer is also eligible.
  • Surgical criteria:
    • a. All Patients with inoperable Stage III or IV disease are eligible.
    • b. All Stage III or IV patients inoperable or with macroscopic residual tumor following primary debulking surgery are eligible
  • Patients must provide blood sample for ctDNA HRR testing at screening. The ctDNA HRR testing results will be used for patient randomization. If gBRCAmut (germline BRCAmut) detected by locally approved tests (i.e. BRACAnalysis CDx™) is previously documented, the patients can be randomized before getting blood ctDNA HRR results. However, blood samples are still required at screening for ctDNA HRR testing.
  • Patients who have undergone PDS must be randomized within a maximum of 6 weeks following surgery. (Note: Optional bevacizumab for each Arm starts in Cycle 2)
  • Patient of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of study treatment.
  • Patient must be postmenopausal, free from menses for >1 year, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 180 days after the last dose of study treatment.
  • Patient must have adequate organ function, defined as follows (Note: Complete blood count test should be obtained without transfusion or receipt of stimulating factors within 2 weeks before obtaining screening blood sample):
    • a. Absolute neutrophil count ≥1,500/μL
    • b. Platelets ≥100,000/μL
    • c. Hemoglobin ≥9 g/dL
    • d. Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation
    • e. Total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 × ULN
    • f. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN unless liver metastases are present, in which case they must be ≤5 × ULN
    • 9. Patient must have an ECOG score of 0 or 1.
    • 10. Patient must have normal blood pressure (BP) or adequately treated and controlled hypertension (systolic BP ≤140 mmHg and/or diastolic BP ≤90 mmHg).
    • 11. Patient must agree to complete PROs (i.e., quality-of-life questionnaires) throughout the study.
    • 12. Patient must be able to take oral medication.
    • 13. Patient must provide archival tumor sample or agree to undergo tumor biopsy at screening for HRD testing.

Number of Patients (Planned) / Nombre de patientes à recrutées

Up to 960 patients will be randomized 1:1:2 into the study.

Criteria for Evaluation / Critère principal d’évaluation

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Efficacy Analysis

Primary Endpoint

The primary efficacy endpoint is PFS, defined as the time from the date of treatment randomization to the date of first documentation of progression or death by any cause in the absence of progression, whichever occurs first, as determined by the Investigator. Progression will be assessed by RECIST v1.1 criteria. In addition, a sensitivity analysis based on blinded central review (BICR) will be conducted as well.

Secondary Endpoints

The following secondary efficacy endpoints will be evaluated:

  • OS, as measured from the date of randomization to the date of death by any cause
  • ORR, defined as the percentage of patients with CR or PR on study treatment as assessed by RECIST v. 1.1
  • DOR, defined as the time from first documentation of CR or PR until the time of first documentation of disease progression (PD) as assessed by RECIST v1.1
  • DCR, defined as the proportion of patients with a best overall response of CR, PR, or SD, as assessed by RECIST v1.1
  • The observed change from baseline and time to symptom worsening in the EORTC-QLQ-C30, EORTC-QLQ-OV28, and EQ-5D-5L PRO assessments
  • TFST, defined as the date of randomization in the current study to the start date of the first subsequent anticancer therapy
  • TSST, defined as the date of randomization in the current study to the start date of the second subsequent anticancer therapy
  • PFS2, defined as the time from randomization to the earlier date of assessment of progression on the next anticancer therapy following study treatment or death by any cause as assessed by the investigator.
  • RECIST v. 1.1 or CA-125 progression-free survival, defined as the date of randomization to the earliest date of progression assessed by RECIST v1.1 or CA-125 progression or death by any cause.

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Modifié le 20-02-2019 14:02