A Correlative Study for Predicting Response and Toxicity in Patients Receiving Chemotherapy for Breast Cancer

Terminated

Interventions: Procedure: Biopsy
Procedure: Serum Collection
Procedure: Urine Collection
Drug: Gemcitabine
Drug: Doxorubicin
Drug: Capecitabine
Drug: Vinorelbine
Drug: Cyclophosphamide

Brief Summary: The proposed trial provides a unique opportunity in that it combines genomic, proteomic, and pharmacogenomic assessments in patients receiving the most commonly used chemotherapies for advanced breast cancer. To date no other trial has analyzed gene and protein expression at the same time points in the same patient, combined with clinical outcome. Similar to previous attempts to predict response based on expression of a single gene or protein, the researchers expect that neither genomic or proteomic profiling alone will be sufficient to optimize therapy. Rather, the researchers expect an iterative process that combines information gleaned from both platforms, modified to avoid toxicity based on pharmacogenomics.

Detailed Description: OUTLINE: This is a 4 arm, multi-center study.

Sample Collection:

* Core Biopsy

* Serum

* Urine

Treatment Regimens (Investigator/Patient Discretion):

* Arm A: Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 1 of every 21-day cycle

* Arm B: Capecitabine 1000 mg/m2 BID days 1-14 of every 21-day cycle

* Arm C: Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle

* Arm D: Gemcitabine 1000 mg/m2 days 1, 8, 15 of every 28-day cycle

Performance status \& Organ Function:

Performance status and organ function appropriate for chemotherapy in the opinion of the treating investigator according to Good Clinical Practice (GCP).

Life Expectancy: Not specified

Hematopoietic: Not specified

Hepatic: Not specified

Renal: Not specified

Cardiovascular: Not specified

Pulmonary: Not specified

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease.
Disease amenable to pre-treatment core or incisional biopsy with adequate tissue for histology and genomic/proteomic analysis.
Measurable disease as assessed within 21 days prior to being registered for protocol therapy by RECIST.
Planned chemotherapy with one of the following regimens:
1. Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 1 of every 21-day cycle
2. Capecitabine 1000 mg/m2 BID days 1-14 of every 21-day cycle
3. Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle
4. Gemcitabine 1000 mg/m2 days 1, 8, 15 of every 28-day cycle

Exclusion Criteria

No serious uncontrolled medical or surgical condition that the investigator feels might compromise study participation.
Negative pregnancy test obtained within 7 days prior to being registered for protocol therapy for women of child bearing potential.
Unwillingness to use adequate contraception (or practicing complete abstinence). Subjects should be advised that adequate contraception (or complete abstinence) must be continued while on treatment and for a period of 3 months after the final dose of chemotherapy.
No breast-feeding.

Arm && Interventions

Group	Intervention	Description
A	Biopsy	Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 2 of every 21-day cycle
B	Biopsy	Capecitabine 1000mg/m2 bid days 1-14 of every 21-day cycle
C	Serum Collection	Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle
C	Urine Collection	Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle
D	Serum Collection	Gemcitabine 1000mg/m2 days 1, 8, 15 of every 28-day cycle
D	Urine Collection	Gemcitabine 1000mg/m2 days 1, 8, 15 of every 28-day cycle
A	Serum Collection	Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 2 of every 21-day cycle
C	Biopsy	Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle
A	Urine Collection	Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 2 of every 21-day cycle
D	Biopsy	Gemcitabine 1000mg/m2 days 1, 8, 15 of every 28-day cycle
B	Serum Collection	Capecitabine 1000mg/m2 bid days 1-14 of every 21-day cycle
B	Urine Collection	Capecitabine 1000mg/m2 bid days 1-14 of every 21-day cycle
D	Gemcitabine	Gemcitabine 1000mg/m2 days 1, 8, 15 of every 28-day cycle
A	Doxorubicin	Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 2 of every 21-day cycle
A	Cyclophosphamide	Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 2 of every 21-day cycle
B	Capecitabine	Capecitabine 1000mg/m2 bid days 1-14 of every 21-day cycle
C	Vinorelbine	Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle

Primary Outcome Measures

Name	Time	Method
To correlate tumor gene expression (genomic profile) with response to commonly used chemotherapies in patients with advanced breast cancer	36 months

Secondary Outcome Measures

Name	Time	Method
To compare serum and tissue proteomic analyses.	36 months
To correlate toxicity and/or response with drug-specific pharmacogenomic parameters.	36 months
To correlate serum and tumor proteomic profiles with response to commonly used chemotherapies.	36 months
To compare genomic and proteomic profiles.	36 months

Locations (11): Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
Baylor College of Medicine - Methodist Breast Center
🇺🇸
Houston, Texas, United States
Arnett Cancer Care
🇺🇸
Lafayette, Indiana, United States
Community Regional Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Mary Lou Mayer, M.D.
🇺🇸
Indianapolis, Indiana, United States
Fort Wayne Oncology & Hematology, Inc
🇺🇸
Fort Wayne, Indiana, United States
Center for Cancer Care at Goshen Health System
🇺🇸
Goshen, Indiana, United States
Horizon Oncology Center
🇺🇸
Lafayette, Indiana, United States
Instituto de Enfermedades Neoplasticas (INEN)
🇵🇪
Lima, Peru
Indiana University Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Cancer Care Center of Southern Indiana
🇺🇸
Bloomington, Indiana, United States