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HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT03685331
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : March 1, 2021
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE September 18, 2018
First Posted Date  ICMJE September 26, 2018
Last Update Posted Date March 1, 2021
Actual Study Start Date  ICMJE October 15, 2020
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
Progression-free survival [ Time Frame: From first dose of protocol therapy to progression or death due to any cause, whichever comes first, an estimated average of 7 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Objective response rate [ Time Frame: From first dose of protocol therapy to progression or death due to any cause, whichever comes first, an estimated average of 7 months ]
    Includes complete and partial response as per RECIST 1.1 criteria. Overall response rate will be defined as the proportion of patients within the efficacy analysis set that experience a complete or partial response.
  • 24-week clinical benefit rate [ Time Frame: From the date of study treatment until the date of progression, an estimated average of 7 months ]
    Defined as the proportion of patients within the efficacy analysis set that experience clinical benefit ≥24 weeks.
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 HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer
Official Title  ICMJE Harnessing Olaparib, Palbociclib and Endocrine Therapy: A Phase I/II Trial of Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer (HOPE)
Brief Summary The main purpose of this research study is to learn whether the investigational combination of olaparib, palbociclib, and fulvestrant is safe in patients with estrogen receptor-positive breast cancer and BRCA1 or BRCA2 mutations.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
The phase I component is a dose-escalation study. Dose escalation will follow a 3+3 design. An additional cohort of at least 36 patients (total number of patients in phase I and phase II = 54) will be included on the single-arm, non-randomized phase II portion of this clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Breast Cancer
  • Locally Advanced Breast Cancer
  • Advanced Breast Cancer
  • BRCA2 Mutation
  • BRCA1 Mutation
Intervention  ICMJE
  • Drug: Palbociclib
    Combination of palbociclib, olaparib, and fulvestrant.
  • Drug: Olaparib
    Combination of palbociclib, olaparib, and fulvestrant.
  • Drug: Fulvestrant
    Combination of palbociclib, olaparib, and fulvestrant.
Study Arms  ICMJE
  • Experimental: Phase I Level 0

    (28-day cycle)

    Olaparib 300 mg by mouth twice a day, days 1-28; fulvestrant 500 mg intramuscularly, Day 1 + 500 mg intramuscularly Cycle 0 Day 15; palbociclib 75 mg by mouth daily, days 1-21, beginning at cycle 1

    Interventions:
    • Drug: Palbociclib
    • Drug: Olaparib
    • Drug: Fulvestrant
  • Experimental: Phase I Level 1

    (28-day cycle)

    Olaparib 300 mg by mouth twice a day, days 1-28; fulvestrant 500 mg intramuscularly, Day 1 + 500 mg intramuscularly Cycle 0 Day 15; palbociclib 100 mg by mouth daily, days 1-21, beginning at cycle 1

    Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal.

    Interventions:
    • Drug: Palbociclib
    • Drug: Olaparib
    • Drug: Fulvestrant
  • Experimental: Phase I Level 2

    (28-day cycle)

    Olaparib 300 mg by mouth twice a day, days 1-28; fulvestrant 500 mg intramuscularly, Day 1 + 500 mg intramuscularly Cycle 0 Day 15; palbociclib 125 mg by mouth daily, days 1-21, beginning at cycle 1

    Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal.

    Interventions:
    • Drug: Palbociclib
    • Drug: Olaparib
    • Drug: Fulvestrant
  • Experimental: Phase II

    (28-day cycle) Olaparib 300 mg by mouth twice a day, days 1-28; fulvestrant 500 mg intramuscularly once monthly on Day 1 of each cycle + 500 mg intramuscularly on Cycle 1 Day 15; palbociclib dose as per maximum tolerated dose determined during Phase I, by mouth daily, days 1-21

    Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal.

    Interventions:
    • Drug: Palbociclib
    • Drug: Olaparib
    • Drug: Fulvestrant
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: September 24, 2018)
54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2024
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females/males ≥ age 18
  • Germline or somatic deleterious or suspected deleterious mutation in BRCA1 or BRCA2
  • Metastatic or locally advanced unresectable breast cancer that is ER and/or PR positive (>1%) and HER2 nonamplified
  • Prior treatment with 0-2 prior lines of chemotherapy for metastatic breast cancer
  • Regarding prior platinum-based chemotherapy:

    1. Patients who received prior platinum-based chemotherapy in the adjuvant or neoadjuvant setting for breast cancer are eligible if treatment was completed at least 12 months prior to diagnosis of metastatic disease.
    2. Patients who received platinum for advanced breast cancer are eligible to enter the study provided there was no evidence of disease progression during the platinum chemotherapy.
    3. Patients who received prior platinum-based as a potentially curative treatment for a prior non-breast cancer (e.g., ovarian cancer) with no evidence of disease for 5 years or greater prior to study entry are permitted.
  • Deemed a candidate for endocrine therapy (any prior endocrine therapy is permitted; no prior endocrine therapy is also permitted)
  • Adequate organ and bone marrow function
  • ECOG performance status 0-1
  • At least one measurable disease or disease that can be assessed by CT or MRI
  • Life expectancy ≥ 16 weeks
  • Postmenopausal as defined below. Women who are on pharmacologic ovarian suppression must have two negative urine or serum pregnancy tests: one during screening (within 28 days prior to study treatment) and one within 7 days prior to commencing treatment.

Postmenopausal is defined as one of the below:

  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
  • radiation-induced oophorectomy with last menses >1 year ago
  • chemotherapy-induced menopause with >1 year interval since last menses
  • bilateral oophorectomy or hysterectomy
  • on luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards as pharmacologic ovarian suppression
  • Female patients of childbearing potential (not post-menopausal as defined above) must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 1 month after last dose of study drug(s) to prevent pregnancy.
  • Male patients and their sexual partners of childbearing potential must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner.
  • Willing to comply with study requirements and procedures including use of appropriate contraception, willingness to discontinue herbal preparations / medications, and study biopsy if archival tissue is not available

Exclusion Criteria:

  • Involvement in study planning or conduct
  • Regarding prior olaparib or palbociclib,

    a) Phase II: Patients who previously progressed on olaparib or palbociclib for metastatic breast cancer treatment are excluded

  • Participation in another clinical study with an investigational product during the last 3 weeks
  • Systemic chemotherapy or radiotherapy (except palliative) within 3 weeks of start of study treatment
  • Major surgery within 2 weeks of start of study treatment
  • Other malignancy within the last 5 years with exceptions listed in the protocol
  • Concomitant strong or moderate CYP3A inhibitors/ inducers
  • Persistent toxicity of prior cancer therapy that is grade ≥ 2 except for alopecia or neuropathy
  • MDS or features suggestive of MDS/AML
  • Symptomatic uncontrolled brain metastases
  • Patients considered to be at poor medical risk
  • QTc >470 msec on 2 or more time points or a family history of long QT syndrome
  • Unable to swallow or absorb oral medication
  • Immunocompromised patients
  • Pregnant or breast-feeding
  • Hypersensitivity to olaparib, palbociclib, fulvestrant, or any excipients of these products
  • Known active hepatitis
  • Prior bone marrow transplant
  • Whole blood transfusions 120 days prior to signing consent
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: Payal Shah, MD 855-216-0098 PennCancerTrials@emergingmed.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03685331
Other Study ID Numbers  ICMJE UPCC 21118
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Abramson Cancer Center of the University of Pennsylvania
Study Sponsor  ICMJE Abramson Cancer Center of the University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Payal Shah, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account Abramson Cancer Center of the University of Pennsylvania
Verification Date February 2021

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