Back to results

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

Primary Purpose

Metastatic Breast Cancer, Locally Advanced Breast Cancer, Advanced Breast Cancer

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Palbociclib

Olaparib

Fulvestrant

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring HER2-negative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Abramson Cancer Center of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Phase I Level 0

Phase I Level 1

Phase I Level 2

Phase II

Arm Description

(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

(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.

(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.

(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.

Outcomes

Primary Outcome Measures

Progression-free survival

Secondary Outcome Measures

Objective response rate

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

Defined as the proportion of patients within the efficacy analysis set that experience clinical benefit ≥24 weeks.

Full Information

NCT ID

NCT03685331

First Posted

September 18, 2018

Last Updated

October 5, 2023

Sponsor

Abramson Cancer Center at Penn Medicine

1. Study Identification

Unique Protocol Identification Number

NCT03685331

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)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 15, 2020 (Actual)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abramson Cancer Center at Penn Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

HER2-negative

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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)

Allocation

Non-Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Phase I Level 0

Arm Type

Experimental

Arm Description

Arm Title

Phase I Level 1

Arm Type

Experimental

Arm Description

Arm Title

Phase I Level 2

Arm Type

Experimental

Arm Description

Arm Title

Phase II

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Intervention Description

Combination of palbociclib, olaparib, and fulvestrant.

Intervention Type

Drug

Intervention Name(s)

Olaparib

Intervention Description

Combination of palbociclib, olaparib, and fulvestrant.

Intervention Type

Drug

Intervention Name(s)

Fulvestrant

Intervention Description

Combination of palbociclib, olaparib, and fulvestrant.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Objective response rate

Description

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

Title

24-week clinical benefit rate

Description

Defined as the proportion of patients within the efficacy analysis set that experience clinical benefit ≥24 weeks.

Time Frame

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Payal D. Shah, MD

Organizational Affiliation

Abramson Cancer Center at Penn Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

35235412

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs