Metastatic Breast CancerPhase 1NCT03685331
HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer
A Phase 1 study testing Palbociclib, Olaparib and Fulvestrant in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer, Locally Advanced Breast Cancer, Advanced Breast Cancer
- What is being tested?
- Palbociclib, Olaparib and Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2020to 1 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- Involvement in study planning or conduct
- Regarding prior olaparib or palbociclib,
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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)
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
- Being tested
- Palbociclib, Olaparib, Fulvestrant
- Keywords
- HER2-negative
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Combination of palbociclib, olaparib, and fulvestrant.
OlaparibDrug
Combination of palbociclib, olaparib, and fulvestrant.
FulvestrantDrug
Combination of palbociclib, olaparib, and fulvestrant.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Palbociclib; Drug: Olaparib; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Measured: 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
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.
Measured: 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
Defined as the proportion of patients within the efficacy analysis set that experience clinical benefit ≥24 weeks.
Measured: From the date of study treatment until the date of progression, an estimated average of 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2018
- Study start15 Oct 2020
- Primary completion1 Aug 2025
- Study completion1 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Payal D. Shah, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03685331
- Sponsor's protocol ID
- UPCC 21118
- Status last verified
- Nov 2025
- First submitted
- 18 Sep 2018
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35235412
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03685331
- Acronym / sponsor ID
- UPCC 21118
- Conditions
- Metastatic Breast Cancer, Locally Advanced Breast Cancer, Advanced Breast Cancer, BRCA2 Mutation, BRCA1 Mutation
- Keywords
- HER2-negative
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 1 Aug 2025 (actual)
- Study completion
- 1 Dec 2025 (actual)
- First posted
- 26 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase I Level 0 | Experimental | Drug: Palbociclib, Drug: Olaparib, Drug: Fulvestrant(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 |
| Phase I Level 1 | Experimental | Drug: Palbociclib, Drug: Olaparib, Drug: Fulvestrant(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. |
| Phase I Level 2 | Experimental | Drug: Palbociclib, Drug: Olaparib, Drug: Fulvestrant(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. |
| Phase II | Experimental | Drug: Palbociclib, Drug: Olaparib, Drug: Fulvestrant(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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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:
Key exclusion criteria (20 listed)
- Involvement in study planning or conduct
- Regarding prior olaparib or palbociclib,
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PalbociclibCombination of palbociclib, olaparib, and fulvestrant. | Drug | Phase I Level 0, Phase I Level 1, Phase I Level 2, Phase II |
| OlaparibCombination of palbociclib, olaparib, and fulvestrant. | Drug | Phase I Level 0, Phase I Level 1, Phase I Level 2, Phase II |
| FulvestrantCombination of palbociclib, olaparib, and fulvestrant. | Drug | Phase I Level 0, Phase I Level 1, Phase I Level 2, Phase II |
Primary outcome
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
2 secondary outcomes
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
24-week clinical benefit rate
Time frame: From the date of study treatment until the date of progression, an estimated average of 7 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Derived from this study: PubMed 35235412Bruno 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Payal D. Shah, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Palbociclib, Olaparib and Fulvestrant in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03685331, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.