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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03685331
Recruitment Status : Not yet recruiting
First Posted : September 26, 2018
Last Update Posted : January 7, 2020
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Locally Advanced Breast Cancer Advanced Breast Cancer BRCA2 Mutation BRCA1 Mutation Drug: Palbociclib Drug: Olaparib Drug: Fulvestrant Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Phase I Level 0

(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
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Olaparib
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Fulvestrant
Combination of palbociclib, olaparib, and fulvestrant.

Experimental: Phase I Level 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.

Drug: Palbociclib
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Olaparib
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Fulvestrant
Combination of palbociclib, olaparib, and fulvestrant.

Experimental: Phase I Level 2

(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
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Olaparib
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Fulvestrant
Combination of palbociclib, olaparib, and fulvestrant.

Experimental: Phase II

(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
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Olaparib
Combination of palbociclib, olaparib, and fulvestrant.

Drug: Fulvestrant
Combination of palbociclib, olaparib, and fulvestrant.




Primary Outcome Measures :
  1. 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 Measures :
  1. 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 ]
    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.

  2. 24-week clinical benefit rate [ Time Frame: From the date of study treatment until the date of progression, an estimated average of 7 months ]
    Defined as the proportion of patients within the efficacy analysis set that experience clinical benefit ≥24 weeks.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03685331


Contacts
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Contact: Payal Shah, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Contact: Payal Shah, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
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Principal Investigator: Payal Shah, MD Abramson Cancer Center of the University of Pennsylvania

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Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03685331    
Other Study ID Numbers: UPCC 21118
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
HER2-negative
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Olaparib
Fulvestrant
Palbociclib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors