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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 : Not yet recruiting
First Posted : September 26, 2018
Last Update Posted : January 7, 2020
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 January 7, 2020
Estimated Study Start Date  ICMJE April 2020
Estimated Primary Completion Date September 2022   (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 Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer
Official Title  ICMJE 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
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2018)
54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2022   (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
  • If the patient has received platinum chemotherapy, it must have been administered in one of the following settings:

    1. Adjuvant or neoadjuvant chemotherapy completed at least 12 months prior to study entry
    2. Platinum chemotherapy for locally advanced unresectable or metastatic breast cancer with no evidence of disease progression during treatment
    3. As potentially curative treatment for a prior non-breast cancer with no evidence of disease for ≥ 5 years
  • Deemed a candidate for endocrine therapy (any prior endocrine therapy is permitted; no prior endocrine therapy is also permitted)
  • Normal organ and bone marrow function
  • ECOG performance status 0-1
  • Life expectancy ≥ 16 weeks
  • Measureable disease or disease that can be assessed by CT or MRI
  • Postmenopausal (amenorrhea for 1+ year without exogenous hormone treatments during this time; pharmacologic ovarian suppression; under 50 with LH and FSH within post-menopausal range; radiation-induced ovarian suppression with >1 year since last menses, chemotherapy-induced menopause with >1 year since last menses, surgical menopause, pharmacologic ovarian suppression)
  • 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
  • Prior treatment with a PARP inhibitor or CDK4/6 inhibitor
  • Participation in another clinical study with an investigational product during the last 3 weeks
  • Major surgery within 2 weeks of study treatment
  • Systemic chemotherapy or radiotherapy (except palliative) within 3 weeks 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 or HIV
  • 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 January 2020

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