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

NCT03685331 | Completed Phase 1 FDA Drug

• 1 other identifier: UPCC 21118
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

HER2-negative

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  From first dose of protocol therapy to progression or death due to any cause, whichever comes first, an estimated average of 7 months

Secondary Outcomes (2)

• Objective response rate

  From first dose of protocol therapy to progression or death due to any cause, whichever comes first, an estimated average of 7 months

• 24-week clinical benefit rate

  From the date of study treatment until the date of progression, an estimated average of 7 months

Study Arms (4)

Phase I Level 0

EXPERIMENTAL

(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

Drug: Palbociclib; Drug: Olaparib; Drug: Fulvestrant

Phase I Level 1

EXPERIMENTAL

(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.

Drug: Palbociclib; Drug: Olaparib; Drug: Fulvestrant

Phase I Level 2

EXPERIMENTAL

(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.

Drug: Palbociclib; Drug: Olaparib; Drug: Fulvestrant

Phase II

EXPERIMENTAL

(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.

Drug: Palbociclib; Drug: Olaparib; Drug: Fulvestrant

Interventions

Palbociclib DRUG

Combination of palbociclib, olaparib, and fulvestrant.

Phase I Level 0; Phase I Level 1; Phase I Level 2; Phase II

Olaparib DRUG

Combination of palbociclib, olaparib, and fulvestrant.

Phase I Level 0; Phase I Level 1; Phase I Level 2; Phase II

Fulvestrant DRUG

Combination of palbociclib, olaparib, and fulvestrant.

Phase I Level 0; Phase I Level 1; Phase I Level 2; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.
• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Bruno L, Ostinelli A, Waisberg F, Enrico D, Ponce C, Rivero S, Blanco A, Zarba M, Loza M, Fabiano V, Amat M, Pombo MT, Noro L, Chacon M, Colo F, Chacon R, Nadal J, Nervo A, Costanzo V. Cyclin-Dependent Kinase 4/6 Inhibitor Outcomes in Patients With Advanced Breast Cancer Carrying Germline Pathogenic Variants in DNA Repair-Related Genes. JCO Precis Oncol. 2022 Mar;6:e2100140. doi: 10.1200/PO.21.00140.

  PMID: 35235412 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; olaparib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Payal D. Shah, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 26, 2018
• Study Start: October 15, 2020
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 9, 2026

Record last verified: 2025-11

Locations

US (1)