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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.

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Niraparib Drug: TSR-042 Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 912 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 24, 2018
Estimated Primary Completion Date : November 30, 2021
Estimated Study Completion Date : July 31, 2023


Arm Intervention/treatment
Placebo Comparator: Arm 1
Standard of care chemotherapy treatment with TSR-042 Placebo, and maintenance treatment of Niraparib Placebo and TSR-042 Placebo.
Drug: Placebo
Capsule with no active drug to mimic Niraparib, or IV fluid with no active drug to mimic TSR-042

Active Comparator: Arm 2
Standard of care chemotherapy treatment with TSR-042 Placebo, and maintenance treatment of Niraparib and TSR-042 Placebo.
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: Placebo
Capsule with no active drug to mimic Niraparib, or IV fluid with no active drug to mimic TSR-042

Experimental: Arm 3
Standard of care chemotherapy treatment with TSR-042, and maintenance treatment of Niraparib and TSR-042.
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).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 5 years ]
    The time from the date of randomization until the date of death by any cause.

  2. 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.

  3. 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").

  4. 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.

  5. 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.

  6. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03602859


Contacts
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Contact: Beth Zaharoff 781-209-5485 bzaharoff@tesarobio.com

  Hide Study Locations
Locations
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United States, Alaska
Alaska Women's Cancer Care Recruiting
Anchorage, Alaska, United States, 99508
United States, California
Kaiser Permanente Los Angeles Medical Center Recruiting
Los Angeles, California, United States, 90027
United States, Connecticut
Hartford Hospital Recruiting
Hartford, Connecticut, United States, 06102
United States, Florida
University of Florida Health Cancer Center Recruiting
Gainesville, Florida, United States, 32608
Cancer Specialists of North Florida Recruiting
Jacksonville, Florida, United States, 32256
United States, Illinois
Northwestern Medicine Cancer Center Delnor Recruiting
Geneva, Illinois, United States, 60134
Midwestern Regional Medical Center Recruiting
Zion, Illinois, United States, 60099
United States, Louisiana
Women's Cancer Care Recruiting
Covington, Louisiana, United States, 70433
Willis-Knighton Cancer Center Recruiting
Shreveport, Louisiana, United States, 71103
United States, Maryland
Holy Cross Hospital Recruiting
Silver Spring, Maryland, United States, 20910
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Baystate Medical Center Recruiting
Springfield, Massachusetts, United States, 01199
UMass Memorial Medical School Recruiting
Worcester, Massachusetts, United States, 01605
United States, Minnesota
Minnesota Oncology Hematology, P.A. Recruiting
Minneapolis, Minnesota, United States, 55404
United States, Montana
Billings Clinic Recruiting
Billings, Montana, United States, 59101
United States, New Jersey
Holy Name Medical Center Recruiting
Teaneck, New Jersey, United States, 07666
United States, New York
Mount Sinai Chelsea Recruiting
New York, New York, United States, 10011
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14620
Stony Brook Cancer Center Recruiting
Stony Brook, New York, United States, 11794
United States, North Carolina
Novant Health Presbyterian Medical Center Recruiting
Charlotte, North Carolina, United States, 28204
United States, Ohio
Aultman Hospital Recruiting
Canton, Ohio, United States, 44710
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Willamette Valley Cancer Center Institute and Research Center Recruiting
Eugene, Oregon, United States, 97401
Kaiser Permanente Northwest Recruiting
Portland, Oregon, United States, 97227
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Rhode Island
Women & Infants Hospital of Rhode Island Recruiting
Providence, Rhode Island, United States, 02905
United States, South Dakota
Avera Cancer Institute Recruiting
Sioux Falls, South Dakota, United States, 57105
United States, Texas
Texas Oncology - Austin Central Recruiting
Austin, Texas, United States, 78731
Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
The Center for Cancer and Blood Disorders Recruiting
Fort Worth, Texas, United States, 76104
Texas Oncology - San Antonio Medical Center Recruiting
San Antonio, Texas, United States, 78240
Texas Oncology- The Woodlands, Gynecologic Oncology Recruiting
The Woodlands, Texas, United States, 77380
Texas Oncology - Tyler Recruiting
Tyler, Texas, United States, 75702
United States, Utah
Community Cancer Trials of Utah Recruiting
Ogden, Utah, United States, 84405
Utah Cancer Specialists Recruiting
Salt Lake City, Utah, United States, 84106
United States, Virginia
Emily Couric Clinical Cancer Center Recruiting
Charlottesville, Virginia, United States, 22903
United States, Washington
Kadlec Regional Medical Center Recruiting
Kennewick, Washington, United States, 99336
Swedish Medical Center Recruiting
Seattle, Washington, United States, 98104
Belgium
Algemeen Ziekenhuis Klina Recruiting
Brasschaat, Antwerpen, Belgium, 2930
Universitaire Ziekenhuis Leuven Recruiting
Leuven, Flemish Brabant, Belgium, 3000
CHU Saint Pierre Recruiting
Brussels, Belgium, 1000
Canada, British Columbia
British Columbia Cancer Agency Vancouver Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Czechia
Fakultni Nemocnice Na Bulovce Recruiting
Praha 8 - Liben, Czechia, 180 81
Denmark
Rigshopitalet Recruiting
Copenhagen, Denmark, 2100
Herlev Hospital Recruiting
Herlev, Denmark, 2730
Sjaellands Universitetshospital, Roskilde Recruiting
Roskilde, Denmark, 4000
Finland
Helsingin ja Uudenmaan sairaanhoitopiiri Recruiting
Helsinki, Finland, 00029
Tampere University Hospital Recruiting
Tampere, Finland, 33520
Turun Yliopistollinen Recruiting
Turku, Finland, 20520
France
Clinique Tivoli Ducos Recruiting
Bordeaux, Aquitaine, France, 33000
Hôpital Privé des Côtes d'Armor Recruiting
Plerin, Bretagne, France, 22190
Hôpital de la Croix Saint-Simon Recruiting
Paris, Ile-de-France, France, 75020
Clinique Clémentville Recruiting
Montpellier, Languedoc-Roussillon, France, 34070
Centre Hospitalier de Cholet Recruiting
Cholet Cedex, Pays De La Loire, France, 49300
Institut Saint Catherine Recruiting
Avignon Cedex 9, Provence Alpes Cote d'Azur, France, 84918
Hopital Privé Jean Mermoz Recruiting
Lyon, Rhone-Alpes, France, 68008
Hopital Jean-Minjoz Recruiting
Besancon, France, 25030
Centre de Lutte Contre le Cancer Francois Baclesse Recruiting
Caen, France, 14000
Centre Georges Francois Leclerc Recruiting
Dijon, France, 21000
Centre Hospitalier Departemental Vendee Recruiting
La Roche-sur-Yon, France, 85925
Centre Jean Bernard - Clinique Victo Hugo Recruiting
Le Mans, France, 72000
Centre de Lutte Contre le Cancer - Centre Oscar Lambret Recruiting
Lille, France, 59000
Centre Hospitalier De Mont De Marsan Recruiting
Mont-de-Marsan, France, 40000
Centre Regional de Lutte contre le Cancer Val d'Aurelle Recruiting
Montpellier, France, 34298
Institut de Cancerologie Lucien Neuwirth Recruiting
Saint Priest en Jarez, France, 42270
Romania
Medisprof SRL Recruiting
Cluj-Napoca, Cluj, Romania, 400051
Centrul de Oncologie Sf. Nectarie Recruiting
Craiova, Dolj, Romania, 200347
SC Oncomed SRL Recruiting
Timisoara, Romania, 300239
Spain
Hospital Universitario Infanta Sofia Recruiting
San Sebastián, Madrid, Spain, 28703
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Complejo Hospitalario de Jaen Recruiting
Jaen, Spain, 23007
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Sponsors and Collaborators
Tesaro, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)

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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03602859     History of Changes
Other Study ID Numbers: 3000-03-005
First Posted: July 27, 2018    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tesaro, Inc.:
FIRST
FIRST trial
Niraparib
TSR-042
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents