Clinical trial NCT01990352: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2013-11-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: DNA is constantly subject to damage from exposures including drugs (including chemotherapy), sunlight and aging. Certain genes in the human body help repair this damage (i.e. BRCA1 and other genes). The purpose of this study is to find out if BRCA1 protein expression has a role in response to chemotherapy drugs.

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)

Primary outcomes:
measure: Overall Response Rate for Metastatic Breast Cancer Patients With Low BRCA1 Protein Expression in Their Tumor, Treated With Pegylated Liposomal Doxorubicin
timeFrame: Start of treatment and repeat imaging done at 9 weeks (± 7 days)
Secondary outcomes:
measure: Progression Free Survival for Patients With Breast Cancer With Low BRCA1 Protein Expression Treated With Pegylated Liposomal Doxorubicin
timeFrame: Start of Treatment until the date of first documented progression or date of death, assessed up to an expected average of 100 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
Study officials:
affiliation: University of Arizona
name: Pavani Chalisani, MD
role: PRINCIPAL_INVESTIGATOR
References: