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Trial record 1 of 1 for:    3000-02-004
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A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03326193
Recruitment Status : Active, not recruiting
First Posted : October 31, 2017
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Brief Summary:
Niraparib is an oral inhibitor of poly adenosine diphosphate-ribose polymerase (PARP)-1 and PARP-2. This study will evaluate safety and efficacy of niraparib combined with bevacizumab as maintenance treatment in participants with advanced (stage IIIB-IV) ovarian cancer, fallopian tube cancer, or primary peritoneal cancer following front-line platinum-based chemotherapy with bevacizumab. Eligible participants who achieve complete response (CR), partial response (PR), or no evidence of disease (NED) following treatment with platinum-based chemotherapy in addition to bevacizumab will be enrolled in the study and will receive maintenance treatment with niraparib (for up to 3 years) combined with bevacizumab (for up to 10 months during the maintenance phase or up to a total of 15 months inclusive of the approximately 5 months of bevacizumab received with chemotherapy) or until disease progression, unacceptable toxicity, participant withdrawal, Investigator's decision, or death, whichever comes first. Participants who have not progressed after 3 years of niraparib maintenance treatment may continue with niraparib beyond 3 years if they are benefiting from treatment, upon consultation with Sponsor.

Condition or disease Intervention/treatment Phase
Ovarian Neoplasms Drug: Niraparib Biological: Bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: This is an open label study
Primary Purpose: Treatment
Official Title: A Phase 2, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Niraparib Combined With Bevacizumab as Maintenance Treatment in Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Following Front-line Platinum-based Chemotherapy With Bevacizumab
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : December 24, 2020
Estimated Study Completion Date : November 19, 2021


Arm Intervention/treatment
Experimental: Participants receiving niraparib+ bevacizumab
Participants will be administered bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute (min) intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib will be administered orally once a day continuously throughout each 21-day cycle. On Day 1 of each cycle, niraparib will be administered upon completion of bevacizumab infusion. The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count.
Drug: Niraparib
Niraparib will be administered orally once a day continuously throughout each 21 day cycle. The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count. Participants with a Baseline actual body weight of greater than equal to (>=) 77 kg and Baseline platelet count of >=150,000/ microliter (μL) will take 300 mg/day (3X100mg) at each dose administration. Participants with a Baseline actual body weight of less than (<) 77 kg and/or Baseline platelet count of <150,000/μL will take 200 mg (2X100 mg) at each dose administration.
Other Name: ZEJULA

Biological: Bevacizumab
Maintenance bevacizumab 15 mg/kg will be administered via a 30-minute IV infusion on Day 1 of every 21-day cycle in the absence of progressive disease (PD), unacceptable toxicity, participant withdrawal, Investigator's decision, or death. Bevacizumab will be administered for up to 10 months during the maintenance phase or up to a total of 15 months inclusive of approximately 5 months of bevacizumab received with chemotherapy.
Other Name: Avastin




Primary Outcome Measures :
  1. Progression free survival (PFS) rate [ Time Frame: At 18 months ]
    PFS is defined as the proportion of participants who have not progressed or died within 18 months after niraparib combined with bevacizumab treatment initiation. Progression will be assessed by response evaluation criteria in solid tumors version 1.1 (RECIST) v1.1 criteria per Investigator assessment.


Secondary Outcome Measures :
  1. PFS by RECIST v 1.1 [ Time Frame: Upto 3 years ]
    PFS is assessed as the time from niraparib combined with bevacizumab treatment initiation to the earlier date of assessment of progression, as assessed by RECIST v1.1 criteria based on Investigator assessment, or death by any cause in the absence of progression.

  2. Overall Survival (OS) [ Time Frame: Upto 3 years ]
    OS is defined as the date of initiation of niraparib treatment in combination with bevacizumab to the date of death by any cause.

  3. RECIST or cancer antigen (CA)-125 PFS [ Time Frame: Upto 3 years ]
    RECIST or CA-125 progression-free survival is defined as the time from initiation of niraparib treatment in combination with bevacizumab to the earliest date of progression assessed by RECIST v1.1. or CA-125 progression or death by any cause.

  4. Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) - Patient Reported Outcome (PRO) [ Time Frame: Baseline and upto 3 years ]
    The FOSI is a validated 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale scored from "not at all" (0) to "very much" (4). The average score will be calculated as an average of the 8 items. The total symptom index is calculated as the total of the 8 symptoms. PROs will be collected every 6 weeks (± 7 days) for 6 months, then every 12 weeks (± 7 days) thereafter while the participant is receiving study treatment. Once a participant discontinues treatment, PRO evaluations will be performed 4 weeks, 8 weeks, 12 weeks, and 24 weeks after treatment discontinuation, regardless of subsequent treatment.

  5. Time to First Subsequent Therapy (TFST) [ Time Frame: Upto 3 years ]
    TFST is defined as the date of initiation of niraparib treatment in combination with bevacizumab treatment in the current study to the start date of the first subsequent anticancer therapy.

  6. Time to Second Subsequent Therapy (TSST) [ Time Frame: Upto 3 years ]
    TSST is defined as the date of initiation of treatment of niraparib in combination with bevacizumab treatment in the current study to the start date of the second subsequent anticancer therapy.

  7. Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Upto 3 years ]
    TEAE is defined as any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

  8. Number of participants with serious adverse events (SAEs) [ Time Frame: Upto 3 years ]
    An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the above outcomes.

  9. Number of participants with AEs leading to discontinuation [ Time Frame: Upto 3 years ]
    Number of participants with AEs leading to discontinuation will be assessed.

  10. Number of participants with dose reduction due to AEs [ Time Frame: Upto 3 years ]
    Number of participants with dose reduction due to AEs will be assessed.

  11. Change from Baseline in eastern cooperative oncology group (ECOG) performance status [ Time Frame: Baseline and upto 3 years. ]
    Performance status will be assessed using the ECOG scale (Grade 0-4). Grade 0 indicates fully active, able to carry on all pre-disease performance without restriction. Grade 4 indicates completely disabled cannot carry on any self-care and totally confined to bed or chair.

  12. Change from Baseline in hemoglobin (grams per deciliter) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for assessment of hemoglobin.

  13. Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (giga cells per Liter) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for the assessment of neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count.

  14. Change from Baseline in mean corpuscular volume (MCV) (picograms) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for mean corpuscular volume assessment.

  15. Change from Baseline in differential white blood cell count (percentage) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for differential white blood cell count assessment.

  16. Change from Baseline in International normalized ratio [ Time Frame: Baseline and upto 3 years. ]
    Blood samples will be collected for assessment of International normalized ratio.

  17. Change from Baseline in activated partial thromboplastin time (seconds) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for assessment of activated partial thromboplastin time.

  18. Change from Baseline in sodium, potassium, calcium magnesium, chloride,glucose, and blood urea nitrogen (BUN) levels (millimoles per liter) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for assessment of sodium, potassium, calcium magnesium, chloride,glucose, and BUN levels.

  19. Change from Baseline in total bilirubin and creatinine levels (micromoles per Liter) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for assessment of total bilirubin and creatinine levels.

  20. Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels (International units per Liter) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for assessment of AST and ALT levels.

  21. Change from Baseline in albumin and total protein levels (gram per Liter) [ Time Frame: Baseline and upto 3 years ]
    Blood samples will be collected for assessment of albumin and total protein levels.

  22. Number of participants with abnormal vital signs [ Time Frame: Upto 3 years ]
    Blood pressure, pulse rate, and temperature and will be measured.

  23. Number of participants with abnormal physical examination. [ Time Frame: Upto 3 years ]
    Physical examination will be performed.

  24. Number of participants receiving concomitant medications [ Time Frame: Upto 3 years ]
    Concomitant medications will be recorded.



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
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must be female, be greater than equal to (>=) 18 years of age, be able to understand the study procedures, and agree to participate in the study by providing written informed consent.
  • Participants must have newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) Stage IIIB to IV epithelial ovarian, fallopian tube, or peritoneal cancer and have recovered from debulking surgery.
  • Participants must have high-grade serous or endometrioid or high-grade predominantly serous or endometrioid histology, regardless of HRD or gBRCA mutation status. Participants with non mucinous epithelial ovarian cancer and gBRCA mutation are eligible.
  • Participants must have completed front-line, platinum-based chemotherapy with CR, PR, or NED and have first study treatment dose within 12 weeks of the first day of the last cycle of chemotherapy:
  • a. A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 9 treatment cycles. Participants who discontinued platinum-based therapy early as a result of non hematologic toxicity specifically related to the platinum regimen (ie, neurotoxicity or hypersensitivity) are eligible if they have received a minimum of 4 cycles of the platinum regimen.
  • b. IV, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed.
  • Participants must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. Participants who undergo interval debulking surgery are eligible if they have received only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy.
  • Participant must have had 1 attempt at optimal debulking surgery.
  • Participant must have either CA-125 in the normal range or CA-125 decrease by more than 90% during front-line therapy that is stable for at least 7 days (ie, no increase > 15% from nadir).
  • Participant must have adequate organ function.
  • Participant must have an ECOG score of 0 or 1.
  • Participant must have normal blood pressure or well-controlled hypertension.
  • Participant must agree to complete PROs (quality of life [QoL] questionnaire) throughout the study, including after study treatment discontinuation.
  • Participant must be able to take oral medication.
  • Participant must agree to undergo tumor HRD testing at screening. The tumor sample must be submitted for HRD testing during the Screening Period. Participants do not have to wait for the HRD test result to be enrolled. If archival tumor tissue is not available for testing, the participant must agree to undergo a fresh biopsy.
  • Participant of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of study treatment.
  • Participants 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 through180 days after the last dose of study treatment.

Exclusion Criteria:

  • Participants with ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any low grade tumors.
  • Participants with clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina < 6 months to enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade II or greater peripheral vascular disease, and history of cerebrovascular accident (CVA) within 6 months).
  • Participants with gastrointestinal disorders or abnormalities that would interfere with absorption of study treatment.
  • History of bowel obstruction, including sub-occlusive disease, related to the underlying disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction.
  • Participant has proteinuria as demonstrated by urine protein:creatinine ratio >= 1.0 at screening or urine dipstick for proteinuria ≥ 2 (participants discovered to have >=2 proteinuria on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate < 2 gram (g) of protein in 24 hours to be eligible).
  • Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML).
  • Participant has received treatment previously with a PARP inhibitor.
  • Other than ovarian cancer, the participant has been diagnosed or treated for invasive cancer less than 5 years prior to study enrollment. Participants with cervical carcinoma in situ, non melanomatous skin cancer, and ductal carcinoma in situ definitively treated are allowed.
  • Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non malignant systemic disease, or active, uncontrolled infection.
  • Participant has known contraindication to PARP inhibitors or (VEGF inhibitors.
  • Participant is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of CVA, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
  • Participant is immunocompromised (patients with splenectomy are allowed).
  • Participant has known, active hepatic disease (ie, hepatitis B or C).
  • Participant has a QT interval prolongation > 480 milliseconds (ms) at screening. If a participant has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation (ie, the participant otherwise has no cardiac abnormalities), then the participant may be eligible to participate in the study following discussion with the Medical Monitor.
  • Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study drug or for 180 days after the last dose of study drug ; additionally, female participant should not breastfeed during treatment with niraparib and for 30 days after receipt of the last dose due to the potential for serious adverse reactions from niraparib in breastfed infants

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): NCT03326193


Locations
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United States, Alabama
GSK Investigational Site
Mobile, Alabama, United States, 36604
United States, Alaska
GSK Investigational Site
Anchorage, Alaska, United States, 99508
United States, Arizona
GSK Investigational Site
Mesa, Arizona, United States, 85284
United States, California
GSK Investigational Site
Burbank, California, United States, 91505
GSK Investigational Site
Los Angeles, California, United States, 90095
United States, Florida
GSK Investigational Site
Fort Myers, Florida, United States, 33908
GSK Investigational Site
Saint Petersburg, Florida, United States, 33705
United States, Kansas
GSK Investigational Site
Kansas City, Kansas, United States, 66103
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48201
GSK Investigational Site
Detroit, Michigan, United States, 48202
United States, Mississippi
GSK Investigational Site
Jackson, Mississippi, United States, 39216
United States, Missouri
GSK Investigational Site
Columbia, Missouri, United States, 65212
GSK Investigational Site
Kansas City, Missouri, United States, 64132
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
GSK Investigational Site
Englewood, New Jersey, United States, 07631
GSK Investigational Site
Morristown, New Jersey, United States, 07962-1956
United States, New York
GSK Investigational Site
Albany, New York, United States, 12208
GSK Investigational Site
Rochester, New York, United States, 14620-4159
United States, North Carolina
GSK Investigational Site
Asheville, North Carolina, United States, 28816
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43214
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
GSK Investigational Site
Providence, Rhode Island, United States, 02905
United States, Tennessee
GSK Investigational Site
Chattanooga, Tennessee, United States, 37403
GSK Investigational Site
Kingsport, Tennessee, United States, 37660
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Fort Worth, Texas, United States, 76104
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Tesaro, Inc.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03326193    
Other Study ID Numbers: 213358
3000-02-004 ( Other Identifier: Tesaro )
First Posted: October 31, 2017    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.:
Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
Ovarian Cancer
Primary Peritoneal carcinoma
Fallopian Tube
Vascular endothelial growth factor (VEGF) inhibitor
Bevacizumab
Niraparib
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
Bevacizumab
Niraparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action