S0500 Treatment Decision Making Based on Blood Levels of Tumor Cells for Metastatic Breast Cancer Treated With Chemo

OBJECTIVES:

Primary

Determine whether women with metastatic breast cancer and elevated circulating tumor cells (CTCs) (≥ 5 per 7.5 mL of whole blood) after 3 weeks of first-line chemotherapy derive increased overall survival from changing to an alternative chemotherapy regimen at the next course rather than waiting for clinical evidence of progressive disease before changing to an alternative chemotherapy regimen.
Determine whether these patients derive increased progression-free survival (PFS) from changing to an alternative chemotherapy regimen at the next course rather than waiting for clinical evidence of progressive disease before changing to an alternative chemotherapy regimen.
Confirm previous findings that patients with < 5 CTCs per 7.5 mL of whole blood on initial screening have longer median OS and PFS than patients with ≥ 5 CTCs per 7.5 mL of whole blood.
Determine the prognostic value of sequentially collected CTC values in these patients.
Compare toxicity between patients with and without elevated CTCs after 3 weeks of first-line chemotherapy AND between the two randomized treatment arms.

Secondary

Compare the prognostic and predictive value of CTC number vs breast cancer tumor markers, including CA 15-3 and carcinoembryonic antigen.
Create a serum specimen bank for future biologic investigation.

OUTLINE: This is a partially blinded, partially randomized, multicenter study. Patients are assigned to 1 of 3 groups based on circulating tumor cells (CTCs) after 1 course of chemotherapy.

All patients undergo blood collection before their first dose of first-line chemotherapy* to determine baseline CTC count. Patients with < 5 CTCs at baseline are assigned to group I. Patients with ≥ 5 CTCs at baseline undergo a second blood draw on day 22 (after completion of 1 course of chemotherapy). Patients with < 5 CTCs after completing 1 course of chemotherapy are assigned to group 2. Patients with ≥ 5 CTCs after completion of 1 course of chemotherapy are assigned to group 3.

NOTE: *Chemotherapy may be initiated while waiting for the baseline CTC result.

Group 1 (low risk of early progression): Patients continue to receive regular treatment without change at the discretion of the physician. Patients are eligible for other first-line chemotherapy trials. No further blood is collected.
Group 2 (moderate risk of early progression): Patients continue to receive their current chemotherapy regimen without change.

Group 3 (high risk of early progression): Patients are stratified according to HER-2 status (positive vs negative) and disease type (bone-only vs measurable disease). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients continue with their current chemotherapy regimen without change.
Arm II: Patients switch to a different chemotherapy regimen. Selection of a new chemotherapy regimen is made by the patient's doctor.

Patients receiving hormonal therapy or biologic therapy and chemotherapy continue to receive the hormonal or biologic therapy unchanged regardless of CTC level.

In groups 2 and 3, blood is collected periodically during chemotherapy and then at the completion of chemotherapy. Samples are examined for CTCs via the CellSearchâ„¢ blood test. Blood is also tested for CA 15-3 and carcinoembryonic antigen (CEA).

After completion of study therapy, patients are followed for up to 5 years.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.