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Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients With Recurrent Ovarian Cancer (OPAL)

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ClinicalTrials.gov Identifier: NCT03574779
Recruitment Status : Recruiting
First Posted : July 2, 2018
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.

Brief Summary:
This study is a phase 2, multi-cohort study, which will assess the safety and efficacy of new treatment combinations in patients with recurrent ovarian cancer.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Niraparib Drug: TSR-042 Drug: Bevacizumab Phase 2

Detailed Description:
This study is a phase 2, multi-cohort study, which assesses the safety (such as AEs, Lab values, etc.) and efficacy of anti-tumor activity of new treatment combinations (niraparib, TSR-042, and bevacizumab in patients with recurrent ovarian cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients With Recurrent Ovarian Cancer
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Cohort A: 1-2 prior lines of therapy
PARP Inhibitor-Naive Platinum-Resistant Ovarian Cancer Treatment Cohort with TSR-042, Bevacizumab, and Niraparib. TSR-042 administered 500mg every 3 weeks for 4 cycles, followed by 1,000 mg every 6 weeks thereafter. Bevacizumab administered 15 mg/kg every 3 weeks for up to 15 months. Niraparib 200 or 300 mg per day.
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: Bevacizumab
Bevacizumab is an FDA approved antiangiogenic recombinant humanized monoclonal Ig G1 antibody against the vascular endothelial growth factor protein, which has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma.
Other Name: Avastin




Primary Outcome Measures :
  1. To evaluate the efficacy of the niraparib combinations defined in each cohort-specific supplement, as assessed by confirmed objective response rate, in patients with advanced, relapsed, high-grade ovarian, fallopian tube, or primary peritoneal cancer. [ Time Frame: From the date of first dose of study treatment until the date of disease progression, date of initiation of new anticancer therapy, or date of death, which ever comes first, assessed up to approximately 3 years. ]
    Confirmed objective response rate, the proportion of patients who have achieved confirmed complete response or partial response, evaluated using RECIST v1.1 based on investigator assessment.


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From the date of first dose of study treatment until the date of disease progression, date of initiation of new anticancer therapy, or date of death, whichever comes first, assessed up to approximately 3 years. ]
    The time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression.

  2. Overall survival [ Time Frame: From the date of first dose of study treatment until the date of death, assessed up to approximately 3 years. ]
    The time from the date of randomization until the date of death from any cause.

  3. Duration of Response [ Time Frame: From the date of first dose of study treatment until the date of disease progression, date of initiation of new anticancer therapy, or date of death, whichever comes first, assessed up to approximately 3 years. ]
    The time from the start date of partial or complete response (whichever is achieved first) to first date recurrence of progressive disease is objectively documented.

  4. Disease Control Rate [ Time Frame: From the date of first dose of study treatment until the date of disease progression, date of initiation of new anticancer therapy, or date of death, whichever comes first, assessed up to approximately 3 years. ]
    The percentage of patients who have achieved complete response, partial response and stable disease.

  5. Cohort A: To evaluate the safety and tolerability in patients treated with TSR-042, bevacizumab, and niraparib. [ Time Frame: From the date of signing the informed consent form until the end of safety follow-up period which is 30 days (adverse events) and 90 days (serious adverse events) after cessation of study treatment, assessed up to approximately 3 years. ]
    Assessment of adverse events and serious adverse events observed throughout the study, and for the safety follow-up period which is 30 days (adverse events) or 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. Assessments will be made using Common Terminology Criteria for Adverse Events (CTCAE v.4.03).



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:

  • Patient has histologically diagnosed high-grade recurrent epithelial (ie, serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer or recurrent carcinosarcoma of the ovary. Patients with high-grade mixed histology are also eligible.
  • Patient has measurable disease according to RECIST v1.1
  • Patient has an ECOG performance status of 0 or 1
  • Patient has adequate organ function, defined as follows:

    1. Absolute neutrophil count ≥1,500/µL
    2. Platelets ≥100,000/µL
    3. Hemoglobin ≥9 g/dL
    4. Serum creatine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Crockcroft-Gault equation.
    5. Total bilirubin ≤1.5x ULN, except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin is ≤1.5x ULN for the direct bilirubin.
    6. Asparate aminotransferase and alanine aminotransferase ≤2.5x ULN, unless liver metastases are present, in which case they must be ≤5x ULN
    7. International normalized ration or prothrombin time (PT) ≤1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
    8. Activated partial thromboplastin time ≤1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Patient of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study treatment, and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment; or patient is of non-childbearing potential.
  • Patient is willing to undergo a pre-treatment tumor biopsy, unless an appropriate archival tumor tissue is available. Additionally, patient must be willing to undergo 1 on-treatment biopsy, provided it is deemed safe and feasible by the Investigator.

For Cohort A, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study:

  • Patient must be resistant to the most recent platinum-based therapy. Patients with primary platinum-refractory disease are not eligible.
  • Patient must not have received any prior therapy for ovarian cancer with a PARP inhibitor.
  • Patient has had 1 to 2 prior lines of anticancer therapy for ovarian cancer.

Exclusion Criteria (Patients will not be eligible for study entry if any of the following criteria are met):

  • Patient has not recovered (ie, to Grade ≤1 or to baseline) from prior chemotherapy-induced adverse events.
  • Patient has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Patient is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment
  • Patient has received prior systemic anticancer therapy including cytotoxic chemotherapy, PARP inhibitor, immune checkpoint inhibitors, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment
  • Patient has received live vaccine within 30 days of planned start of study therapy
  • Patient has symptomatic uncontrolled brain or leptomeningeal metastases
  • Patient had major surgery within 4 weeks of starting the study
  • Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the investigator
  • Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection
  • Patient has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, might interfere with the patient's participation for the full duration of the study treatment, or is not in the best interest of the patient to participate
  • Patient has known active hepatitis B or hepatitis C

For Cohort A, patients will not be eligible for study entry if the following additional exclusion criteria are met:

  • Patient has known hypersensitivity to TSR-042, bevacizumab, niraparib, their components, or their excipients
  • Patient has a known history of myelodysplastic syndrome or acute myeloid leukemia
  • Patient has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
  • Patient received prior treatment with an anti-PI-1 or anti-PD-L1 agent
  • Patient has received prior treatment with anti-angiogenic therapy with the exception of bevacizumab.
  • Patient has bowel obstruction, had bowel obstruction within the past 3 months, or is otherwise judged by the Investigator to be at high risk for bowel obstruction related to the underlaying disease.
  • Patient has proteinuria as demonstrated by urine protein: creatine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2
  • Patient 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 hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months)
  • Patient has a history of recent major thromboembolic event defined as follows:

    1. Pulmonary embolism diagnosed within 3 months of enrollment
    2. Lower extremity deep venous thrombosis diagnosed within 3 months of enrollment

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): NCT03574779


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

Locations
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United States, Alabama
University of Alabama - Birmingham Recruiting
Birmingham, Alabama, United States, 35249
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Stanford University Recruiting
Palo Alto, California, United States, 94304
United States, Connecticut
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06511
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Tesaro, Inc.

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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03574779     History of Changes
Other Study ID Numbers: 3000-02-005
First Posted: July 2, 2018    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 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.:
PARP Inhibitor
OPAL
OPAL Clinical Trial
OPAL Study

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