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

Study Overview
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Brief Summary
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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
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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

Official Title
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Predicting Response and Toxicity in Patients Receiving Chemotherapy for Breast Cancer: A Multicenter Genomic, Proteomic and Pharmacogenomic Correlative Study: Hoosier Oncology Group COE-01

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: Biopsy
* Procedure: Serum Collection
* Procedure: Urine Collection
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: Capecitabine
* Drug: Vinorelbine
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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: Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 1 of every 21-day cycle Capecitabine 1000 mg/m2 BID days 1-14 of every 21-day cycle Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A<br>Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 day 2 of every 21-day cycle | Procedure: Biopsy<br>* core biopsy<br>Procedure: Serum Collection<br>* serum collection<br>Procedure: Urine Collection<br>* urine collection<br>Drug: Doxorubicin<br>* Doxorubicin 60 mg/m2 day 1 of every 21-day cycle<br>Drug: Cyclophosphamide<br>* Cyclophosphamide 600 mg/m2 day 1 of every 21-day cycle<br>|
| B<br>Capecitabine 1000mg/m2 bid days 1-14 of every 21-day cycle | Procedure: Biopsy<br>* core biopsy<br>Procedure: Serum Collection<br>* serum collection<br>Procedure: Urine Collection<br>* urine collection<br>Drug: Capecitabine<br>* Capecitabine 1000 mg/m2 bid days 1-14 of every 21-day cycle<br>|
| C<br>Vinorelbine 25 mg/m2 days 1, 8, 15 of every 28-day cycle | Procedure: Biopsy<br>* core biopsy<br>Procedure: Serum Collection<br>* serum collection<br>Procedure: Urine Collection<br>* urine collection<br>Drug: Vinorelbine<br>* Vinorelbine 25mg/m2 days 1, 8, 15 of every 28-day cycle<br>|
| D<br>Gemcitabine 1000mg/m2 days 1, 8, 15 of every 28-day cycle | Procedure: Biopsy<br>* core biopsy<br>Procedure: Serum Collection<br>* serum collection<br>Procedure: Urine Collection<br>* urine collection<br>Drug: Gemcitabine<br>* Gemcitabine 1000mg/m2 days 1, 8, 15 of every 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate tumor gene expression (genomic profile) with response to commonly used chemotherapies in patients with advanced breast cancer |  | 36 months | 

Secondary Outcome Measures

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