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.
Title
- Brief Title: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, Hormone Receptor-positive, HER2-negative Metastatic Breast Cancer
- Official Title: 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
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
| Drug | Synonyms | Arms |
|---|
| Palbociclib | | Phase I Level 0 |
| Olaparib | | Phase I Level 0 |
| Fulvestrant | | Phase 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
| Name | Type | Description | Interventions |
|---|
| 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 | - Palbociclib
- Olaparib
- 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. | - Palbociclib
- Olaparib
- 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. | - Palbociclib
- Olaparib
- 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. | - 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
- 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
| 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: | Not yet recruiting |
| Lead Sponsor: | Abramson Cancer Center of the University of Pennsylvania |
Trial Keywords
Last Updated
