Clinical Trials /

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

NCT03685331

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UPCC 21118
  • NCT ID: NCT03685331

Conditions

  • Metastatic Breast Cancer
  • Locally Advanced Breast Cancer
  • Advanced Breast Cancer
  • BRCA2 Mutation
  • BRCA1 Mutation

Interventions

DrugSynonymsArms
PalbociclibPhase I Level 0
OlaparibPhase I Level 0
FulvestrantPhase I Level 0

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I Level 0Experimental(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
  • Palbociclib
  • Olaparib
  • Fulvestrant
Phase I Level 1Experimental(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.
  • Palbociclib
  • Olaparib
  • Fulvestrant
Phase I Level 2Experimental(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.
  • Palbociclib
  • Olaparib
  • Fulvestrant
Phase IIExperimental(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.
  • Palbociclib
  • Olaparib
  • Fulvestrant

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure:24-week clinical benefit rate
Time Frame:From the date of study treatment until the date of progression, an estimated average of 7 months
Safety Issue:
Description:Defined as the proportion of patients within the efficacy analysis set that experience clinical benefit ≥24 weeks.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Trial Keywords

  • HER2-negative

Last Updated

July 21, 2021