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Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pegylated liposomal doxorubicin
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Metastatic breast cancer and have formalin-fixed, paraffin embedded primary tumor available for testing BRCA1 protein expression
  • Adults over 18 years of age
  • Have resolution of all acute toxic effects of any prior chemotherapy or radiotherapy to NCI CTC grade ≤ 1 prior to study registration.
  • Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures
  • Be willing and able to comply with the treatment plan, scheduled clinic visits, laboratory and oncological tests and other study procedures
  • Have a ECOG performance status of 0 - 2
  • Measurable disease by CT by RECIST 1.1 to evaluate response
  • Adequate bone marrow function defined as platelets 100 X 109 cells/L, neutrophils 1.5 x 109 cells/L, white blood cells (WBC) 3.0 x 109 cells/L and a hemoglobin 90 gm/L
  • Creatinine < 1.5 mg/dl or creatinine clearance > 40 ml/min
  • Liver function tests (AST and or ALT) should be 2 x upper limit of normal (ULN, defined as per laboratory where blood testing is done), total bilirubin 1.5 x ULN (except for patients with liver metastases, ALT and/or ALT 5 times the upper limit of normal is accepted)

Exclusion Criteria:

  • Myocardial infarction within 6 months of registration
  • Brain metastases unless documented to be controlled post completion of local therapy (surgery and/or radiation therapy) for at least four weeks prior to registration
  • Pregnant or breast feeding women. Women with child bearing potential must use effective measures to prevent pregnancy while receiving pegylated liposomal doxorubicin
  • Have a concurrent active non-breast malignancy except for non-melanoma skin cancer
  • Her2 positive tumors as defined by FDA guidelines(3+ immunohistochemical staining, defined as uniform, intense membrane staining of more than 10% of invasive tumor cells, and for cases with 2+ staining showing gene amplification by FISH, expressed as a ratio of more than 2 when comparing HER-2 gene and chromosome 17 fluorescent signals)

Sites / Locations

  • University of Arizona Cancer Center
  • University of New Mexico Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pegylated liposomal doxorubicin

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate for metastatic breast cancer patients with low BRCA1 protein expression in their tumor, treated with pegylated liposomal doxorubicin
Evaluating if low BRCA1 protein expression has a preferential effect on response when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls. Response rate is defined as the percentage of evaluable patients who achieve complete response (CR) or partial response (PR) as measured by RECIST 1.1 on CT or PET/CT as the best overall response.

Secondary Outcome Measures

Progression free survival for patients with breast cancer with low BCRCA1 protein expression treated with pegylated liposomal doxorubicin
Evaluating if low BRCA1 protein expression has a preferential effect on tumor progression when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls. Progression free survival will be measured as the times from the start of pegylated liposomal doxorubicin to the time the patient is first recorded as having disease progression or dies. If a patient does not progress or die while being followed via tumor assessment, progression-free survival will be censored at the time of last disease assessment. The median progression free survival will be calculated in patients with low BRCA1 protein expression and intact BRCA1 protein expression. Median progression free survival will be estimated by Kaplan-Meier methodology

Full Information

First Posted
November 8, 2013
Last Updated
July 27, 2023
Sponsor
University of Arizona
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1. Study Identification

Unique Protocol Identification Number
NCT01990352
Brief Title
Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy
Official Title
A Single Arm Phase II Trial to Assess Association of BRCA1 Protein Expression With Overall Response Rate in Patients With Metastatic Breast Cancer on Pegylated Liposomal Doxorubicin
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
The PI determined that study specimens being obtained did not yield sufficient data to analyze the prespecified outcome measures and decided to terminate the study prior to meeting enrollment goals.
Study Start Date
November 5, 2013 (Actual)
Primary Completion Date
December 31, 2022 (Actual)
Study Completion Date
December 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary Objective: To evaluate if low BRCA1 protein expression has a preferential effect on response when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls Secondary Objective: To evaluate if low BRCA1 protein expression has a preferential effect on tumor progression when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pegylated liposomal doxorubicin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pegylated liposomal doxorubicin
Primary Outcome Measure Information:
Title
Overall response rate for metastatic breast cancer patients with low BRCA1 protein expression in their tumor, treated with pegylated liposomal doxorubicin
Description
Evaluating if low BRCA1 protein expression has a preferential effect on response when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls. Response rate is defined as the percentage of evaluable patients who achieve complete response (CR) or partial response (PR) as measured by RECIST 1.1 on CT or PET/CT as the best overall response.
Time Frame
Start of treatment and repeat imaging done at 9 weeks (± 7 days)
Secondary Outcome Measure Information:
Title
Progression free survival for patients with breast cancer with low BCRCA1 protein expression treated with pegylated liposomal doxorubicin
Description
Evaluating if low BRCA1 protein expression has a preferential effect on tumor progression when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls. Progression free survival will be measured as the times from the start of pegylated liposomal doxorubicin to the time the patient is first recorded as having disease progression or dies. If a patient does not progress or die while being followed via tumor assessment, progression-free survival will be censored at the time of last disease assessment. The median progression free survival will be calculated in patients with low BRCA1 protein expression and intact BRCA1 protein expression. Median progression free survival will be estimated by Kaplan-Meier methodology
Time Frame
Start of Treatment until the date of first documented progression or date of death, assessed up to an expected average of 100 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Metastatic breast cancer and have formalin-fixed, paraffin embedded primary tumor available for testing BRCA1 protein expression Adults over 18 years of age Have resolution of all acute toxic effects of any prior chemotherapy or radiotherapy to NCI CTC grade ≤ 1 prior to study registration. Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures Be willing and able to comply with the treatment plan, scheduled clinic visits, laboratory and oncological tests and other study procedures Have a ECOG performance status of 0 - 2 Measurable disease by CT by RECIST 1.1 to evaluate response Adequate bone marrow function defined as platelets 100 X 109 cells/L, neutrophils 1.5 x 109 cells/L, white blood cells (WBC) 3.0 x 109 cells/L and a hemoglobin 90 gm/L Creatinine < 1.5 mg/dl or creatinine clearance > 40 ml/min Liver function tests (AST and or ALT) should be 2 x upper limit of normal (ULN, defined as per laboratory where blood testing is done), total bilirubin 1.5 x ULN (except for patients with liver metastases, ALT and/or ALT 5 times the upper limit of normal is accepted) Exclusion Criteria: Myocardial infarction within 6 months of registration Brain metastases unless documented to be controlled post completion of local therapy (surgery and/or radiation therapy) for at least four weeks prior to registration Pregnant or breast feeding women. Women with child bearing potential must use effective measures to prevent pregnancy while receiving pegylated liposomal doxorubicin Have a concurrent active non-breast malignancy except for non-melanoma skin cancer Her2 positive tumors as defined by FDA guidelines(3+ immunohistochemical staining, defined as uniform, intense membrane staining of more than 10% of invasive tumor cells, and for cases with 2+ staining showing gene amplification by FISH, expressed as a ratio of more than 2 when comparing HER-2 gene and chromosome 17 fluorescent signals)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pavani Chalisani, MD
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85742
Country
United States
Facility Name
University of New Mexico Comprehensive Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States

12. IPD Sharing Statement

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Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy

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