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Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer (TOPACIO)

This study is currently recruiting participants.
Verified August 2017 by Tesaro, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02657889
First Posted: January 18, 2016
Last Update Posted: August 25, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Tesaro, Inc.
  Purpose
This Phase 1/2 study will evaluate the safety and efficacy of combination treatment with niraparib and pembrolizumab (MK-3475) in patients with advanced or metastatic triple-negative breast cancer or recurrent ovarian cancer. (KEYNOTE-162)

Condition Intervention Phase
Triple Negative Breast Cancer Ovarian Cancer Breast Cancer Metastatic Breast Cancer Advanced Breast Cancer Stage IV Breast Cancer Fallopian Tube Cancer Peritoneal Cancer Drug: niraparib Biological: pembrolizumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Clinical Study of Niraparib in Combination With Pembrolizumab (MK-3475) in Patients With Advanced or Metastatic Triple-Negative Breast Cancer and in Patients With Recurrent Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Tesaro, Inc.:

Primary Outcome Measures:
  • Evaluate dose-limiting toxicities (DLTs) of combination treatment with niraparib and pembrolizumab during the first cycle of treatment, and to establish a recommended Phase 2 dose (RP2D) and schedule [ Time Frame: Phase 1: Approximately 9 months ]
  • To estimate the clinical activity of combination treatment with niraparib and pembrolizumab in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Phase 2: Approximately 12 months ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of combination treatment with niraparib and pembrolizumab using Common Terminology Criteria for Adverse Events (CTCAE, v4.03) [ Time Frame: Approximately 18 months ]
  • Overall Response Rate (ORR) [ Time Frame: Approximately 12 months ]
    as measured by immune-related RECIST (irRECIST)

  • Duration of Response (DOR) [ Time Frame: Approximately 18 months ]
    defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression

  • Disease Control Rate (DCR) [ Time Frame: Approximately 12 months ]
    defined as the percentage of patients who have achieved CR, PR, or stable disease (SD) per RECIST or irRECIST

  • Progression Free Survival (PFS) [ Time Frame: Approximately 18 months ]
    defined as the time from first dose to the earlier date of assessment of progression, or death by any cause in the absence of progression, by RECIST or irRECIST

  • Overall Survival (OS) [ Time Frame: Approximately 2 years ]
    as measured from the date of first dose to the date of death by any cause

  • To evaluate the Area Under the Curve (AUC), Minimum concentration (Cmin) [ Time Frame: Approximately 9 months ]
  • Maximum Concentration (Cmax) [ Time Frame: Approximately 9 months ]
  • Clearance after oral administration (CL/F) [ Time Frame: Approximately 9 months ]
  • Volume of Distribution after oral administration (Vz/F) [ Time Frame: Approximately 9 months ]
  • AUC at steady state (AUCss) [ Time Frame: Approximately 9 months ]
  • Cmin at steady state (Cmin,ss) [ Time Frame: Approximately 9 months ]
    and Cmax at steady state (Cmax,ss)

  • Cmax at steady state (Cmax,ss) [ Time Frame: Approximately 9 months ]

Estimated Enrollment: 114
Study Start Date: March 2016
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: niraparib plus pembrolizumab

Phase 1: Dose-escalation: ascending doses of niraparib up to 300mg/day orally (PO) on Days 1-21 and pembrolizumab 200mg intravenously (IV) on Day 1 of each 21-day cycle

Phase 2: niraparib (recommended Phase 2 dose) in combination with pembrolizumab 200mg IV on Day 1 of each 21-day cycle

Drug: niraparib Biological: pembrolizumab

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Patient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type:

    1. Phase 1 patients (breast or ovarian cancer)

      • Patients with advanced or metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC). Patients with advanced or metastatic disease may have up to 4 lines of cytotoxic therapy. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy.
      • Patients must have any epithelial (ie, serous, endometroid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have received up to 5 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy.
    2. Phase 2 patients (breast or ovarian cancer)

      • Patients with advanced or metastatic breast cancer must have TNBC. Patients with advanced or metastatic disease may have received up to 2 lines of cytotoxic therapy. Adjuvant and/or neoadjuvant therapies are not counted in the number of lines of therapy. TNBC patients who have previously received platinum chemotherapy in the metastatic setting are allowed to enroll in the study as long as they did not progress while on or within 8 weeks from the day of the last platinum administration.
      • Patients must have with high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have had up to 4 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy.
  • Archival tumor tissue available or a fresh biopsy must be obtained prior to study treatment initiation
  • Measurable lesions by RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) 0 or 1
  • Adequate organ function
  • Able to take oral medications
  • Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours of taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment
  • Male patient agrees to use an adequate method of contraception

Main Exclusion Criteria:

  • Patients with primary platinum refractory ovarian cancer (ie, progressive disease on or within 6 months of first-line platinum therapy)
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Note: Patients previously treated for brain metastases may be able to participate provided they are stable
  • 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 cervical cancer
  • Poor medical risk
  • Condition (such as transfusion dependent anemia or thrombocytopenia), 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.
  • Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study
  • Immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Known active hepatitis B or hepatitis C
  • 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, etc.) is not considered a form of systemic treatment
  • Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor
  • Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening
  • Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
  Contacts and Locations
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): NCT02657889


Contacts
Contact: Clinical Trial Management Group nirap-pembro.combostudy@tesarobio.com

  Show 30 Study Locations
Sponsors and Collaborators
Tesaro, Inc.
Merck Sharp & Dohme Corp.
Investigators
Study Director: Bruce Dezube, MD Tesaro, Inc.
  More Information

Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT02657889     History of Changes
Other Study ID Numbers: 3000-PN162-01-001
First Submitted: January 8, 2016
First Posted: January 18, 2016
Last Update Posted: August 25, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Tesaro, Inc.:
PARP inhibitor
PD-1
Niraparib
Pembrolizumab
Keynote
TOPACIO

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Fallopian Tube Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Pembrolizumab
Niraparib
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action