Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy

NCT01990352 | Terminated Phase 2 Results DMC

• 1 other identifier: 1300000710
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Start of treatment and repeat imaging done at 9 weeks (± 7 days)

Secondary Outcomes (1)

• Progression Free Survival for Patients With Breast Cancer With Low BRCA1 Protein Expression Treated With Pegylated Liposomal Doxorubicin

  Start of Treatment until the date of first documented progression or date of death, assessed up to an expected average of 100 weeks

Study Arms (1)

Pegylated liposomal doxorubicin

EXPERIMENTAL

The enrolled patients will be treated with pegylated liposomal doxorubicin at 30mg/m2 every 21 days.

Drug: Pegylated liposomal doxorubicin

Interventions

Pegylated liposomal doxorubicin DRUG

Doxil will be administered intravenously at 30mg/m2 on days 1 of a 21 day cycle.

Also known as: Doxil

Pegylated liposomal doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (2)

University of Arizona Cancer Center

Tucson, Arizona, 85742, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

liposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The trial was started with preliminary data on BRCA1 immunohistochemistry assay developed with a collaborator. The assay, in the trial, due to differences in the timeline on when the tumor tissue was collected, the variability in the tumor tissue processing, storage, and age of the samples, the assay did not work on the samples as projected. Subsequently, due to COVID-19 and the challenges with the assay performance, the collaborator discontinued further development of the assay.

Results Point of Contact

• Title: Dr. Pavani Chalasani
• Organization: George Washington Cancer Center

pavani.chalasani@email.gwu.edu

(202)-741-2277

Study Officials

• Pavani Chalisani, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2013
• First Posted: November 21, 2013
• Study Start: November 5, 2013
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: November 21, 2023
• Results First Posted: October 26, 2023

Record last verified: 2023-11

Locations

US (2)