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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 (FIRST)

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ClinicalTrials.gov Identifier: NCT03602859
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : April 5, 2019
Sponsor:
Collaborator:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE June 28, 2018
First Posted Date  ICMJE July 27, 2018
Last Update Posted Date April 5, 2019
Actual Study Start Date  ICMJE October 24, 2018
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
Progression Free Survival [ Time Frame: Up to 5 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03602859 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • Overall Survival [ Time Frame: Up to 5 years ]
    The time from the date of randomization until the date of death by any cause.
  • Assessment of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 5 years ]
    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.
  • Time to deterioration in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) [ Time Frame: Up to 5 years ]
    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").
  • 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 ]
    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.
  • 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 ]
    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.
  • Objective Response Rate [ Time Frame: Up to 5 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Drug: Niraparib
    Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.
    Other Name: ZEJULA
  • Drug: TSR-042
    TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).
  • Drug: Placebo
    Capsule with no active drug to mimic Niraparib, or IV fluid with no active drug to mimic TSR-042
Study Arms  ICMJE
  • Placebo Comparator: Arm 1
    Standard of care chemotherapy treatment with TSR-042 Placebo, and maintenance treatment of Niraparib Placebo and TSR-042 Placebo.
    Intervention: Drug: Placebo
  • Active Comparator: Arm 2
    Standard of care chemotherapy treatment with TSR-042 Placebo, and maintenance treatment of Niraparib and TSR-042 Placebo.
    Interventions:
    • Drug: Niraparib
    • Drug: Placebo
  • Experimental: Arm 3
    Standard of care chemotherapy treatment with TSR-042, and maintenance treatment of Niraparib and TSR-042.
    Interventions:
    • Drug: Niraparib
    • Drug: TSR-042
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2019)
912
Original Estimated Enrollment  ICMJE
 (submitted: July 18, 2018)
960
Estimated Study Completion Date  ICMJE July 31, 2023
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Beth Zaharoff 781-209-5485 bzaharoff@tesarobio.com
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   Denmark,   Finland,   France,   Romania,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03602859
Other Study ID Numbers  ICMJE 3000-03-005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE European Network of Gynaecological Oncological Trial Groups (ENGOT)
Investigators  ICMJE Not Provided
PRS Account Tesaro, Inc.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP