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A Phase 3 Comparison of Platinum-Based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-Based Therapy as First-Line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

NCT03602859

Description:

This is a global, multicenter, randomized, double-blind, controlled Phase 3 study in patients with newly diagnosed, Stage III or IV non mucinous epithelial ovarian, fallopian tube, or peritoneal cancer (collectively referred to as "ovarian cancer"). The currently recommended standard of care therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab.

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Ovarian Epithelial Tumor
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Phase 3 Comparison of Platinum-Based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-Based Therapy as First-Line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer
  • Official Title: ENGOT-0V44 The FIRST (First-line Ovarian Cancer Treatment With Niraparib Plus TSR-042) Study: A Randomized, Double-Blind, Phase 3 Comparison of Platinum-Based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-Based Therapy as First-Line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 3000-03-005
  • NCT ID: NCT03602859

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
NiraparibZEJULAArm 2
TSR-042Arm 3
PlaceboArm 1

Purpose

This is a global, multicenter, randomized, double-blind, controlled Phase 3 study in patients with newly diagnosed, Stage III or IV non mucinous epithelial ovarian, fallopian tube, or peritoneal cancer (collectively referred to as "ovarian cancer"). The currently recommended standard of care therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab.

Trial Arms

NameTypeDescriptionInterventions
Arm 1Placebo ComparatorStandard of care chemotherapy treatment with TSR-042 Placebo, and maintenance treatment of Niraparib Placebo and TSR-042 Placebo.
  • Placebo
Arm 2Active ComparatorStandard of care chemotherapy treatment with TSR-042 Placebo, and maintenance treatment of Niraparib and TSR-042 Placebo.
  • Niraparib
  • Placebo
Arm 3ExperimentalStandard of care chemotherapy treatment with TSR-042, and maintenance treatment of Niraparib and TSR-042.
  • Niraparib
  • TSR-042

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a histologically confirmed diagnosis of high-grade nonmucinous
             epithelial ovarian cancer (serous, endometrial, clear cell, carcinosarcoma, an mixed
             pathologies) that is Stage III or IV according to the International Federation of
             Gynecology and Obstetrics (FIGO) or tumor, node and metastasis staging criteria.

          -  All patients with Stage IV disease are eligible. This includes those with inoperable
             disease, those who undergo primary debulking surgery (complete cytoreduction (CC0) or
             macroscopic disease), or those for whom neoadjuvant chemotherapy is planned.

          -  Patients with Stage III are eligible if they meet one or more of the following
             criteria:

               1. High risk Stage IIIC disease.

               2. Planning to receive neoadjuvant chemotherapy.

          -  Patients must provide a blood sample for research at Screening.

          -  Patient must provide a formalin-fixed paraffin embedded tumor tissue sample at
             Screening for research.

          -  Patients must have adequate organ function (Note: complete blood count test should be
             obtained without transfusion or receipt of stimulating factors within 2 weeks before
             obtaining Screening blood sample)

          -  Patients must have an ECOG score of 0 or 1.

          -  Patients must have normal BP or adequately treated and controlled hypertension
             (systolic BP ≤140 mmHg and/or diastolic BP ≤90 mmHg).

          -  Patients must agree to complete HRQoL questionnaires throughout the study.

          -  Patients must be able to take oral medication.

        Exclusion Criteria:

          -  Patient has mucinous, germ cell, transitional cell, or undifferentiated tumor.

          -  Patient has low-grade or Grade 1 epithelial ovarian cancer.

          -  Stage III patient with complete cytoreduction (CC0) resection after primary debulking
             surgery (ie, no macroscopic residual disease, unless the patient has aggregate 5 cm
             extra-pelvic disease during primary debulking surgery.

          -  Patient has not adequately recovered from prior major surgery.

          -  Patient has a known condition, therapy, or laboratory abnormality that might confound
             the study results or interfere with the patient's participation for the full duration
             of the study treatment in the opinion of the Investigator.

          -  Patient has been diagnosed and/or treated with any therapy for invasive cancer <5
             years from study enrollment, completed adjuvant chemotherapy and/or targeted therapy
             (eg, trastuzumab) less than 3 years from enrollment, or completed adjuvant hormonal
             therapy less than 4 weeks from enrollment. Patients with definitively treated
             non-invasive malignancies such as cervical carcinoma in situ, ductal carcinoma in
             situ, Grade 1 or 2, Stage IA endometrial cancer, or non-melanomatous skin cancer are
             allowed.

          -  Patient is at increased bleeding risk due to concurrent conditions (eg, major injuries
             or major surgery within the past 28 days prior to start of study treatment and/or
             history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or
             clinically significant hemorrhage within the past 3 months).

          -  Patient is immunocompromised. Patients with splenectomy are allowed. Patients with
             well-controlled known human immunodeficiency virus (HIV) are allowed.

          -  Patient has known active hepatitis B (eg, hepatitis B surface antigen reactive) or
             hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] is detected).

          -  Patient is considered a poor medical risk due to a serious, uncontrolled medical
             disorder, non-malignant systemic disease, or active, uncontrolled infection.

          -  Patient has had investigational therapy administered within 4 weeks or within a time
             interval less than at least 5 half-lives of the investigational agent, whichever is
             longer, prior to the first scheduled day of dosing in this study.

          -  Patient has received a live vaccine within 14 days of planned start of study therapy.
             Seasonal influenza vaccines that do not contain live viruses are allowed.

          -  Patient has a known contraindication or uncontrolled hypersensitivity to the
             components of paclitaxel, carboplatin, niraparib, bevacizumab, TSR-042, or their
             excipients.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:To compare the progression free survival of patients with Stage III or IV nonmucinous epithelial ovarian cancer treated with platinum-based therapy, TSR-042, and niraparib to standard of care platinum-based therapy as first-line treatment. Progression free survival is defined as the time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression. Progression free survival will be evaluated by Investigator assessment per RECIST v.1.1 criteria.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Up to 5 years
Safety Issue:
Description:The time from the date of randomization until the date of death by any cause.
Measure:Assessment of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame:Up to 5 years
Safety Issue:
Description:Assessment of the percentage of participants with adverse events and serious adverse events observed throughout the study, and for 30 days (adverse events), 90 days (serious adverse events) after cessation of study treatment, or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy.
Measure:Time to deterioration in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)
Time Frame:Up to 5 years
Safety Issue:
Description:EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in patients across diseases. EQ-5D-5L consists of a descriptive section of 5 questions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Questions use a 5-point scale ("no problems", "slight problems", "moderate problems", "severe problems", "unable/extreme problems"). Scores are converted to an index value based on country-specific value sets, with a value of 0 representing "death" and 1 representing "perfect health"). The EQ-5D-5L also includes a visual-analogue scale of overall health on a 100-point scale (from "Worst imaginable health state" to "Best imaginable health state").
Measure:Time to deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30)
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in patients with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/quality of life scale (GHS/QOL), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-C30 employs a week recall period for all items and a 4-point scale for the functional and symptom scales/items with response categories "Not at all", "A little", "Quite a bit" and "Very much". The two items assessing GHS/QOL utilize a 7-point scale ranging from 1 ("Very Poor") to 7 ("Excellent"). Scores are averaged, and transformed to a 0-100 scale. A higher score on functional scales represents better function, and on symptom scales represents more severe symptoms.
Measure:Time to deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Ovarian Cancer (EORTC QLQ-OV28)
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC QLQ-OV28 is a validated questionnaire to assess the overall health-related quality of life in patients with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste. Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment.
Measure:Objective Response Rate
Time Frame:Up to 5 years
Safety Issue:
Description:The percentage of patients with complete response or partial response on study treatment as assessed by RECIST v.1.1 criteria for patients with measurable disease. Objective response rate will also be assessed per irRECIST criteria.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • FIRST
  • FIRST trial
  • Niraparib
  • TSR-042

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