Trial Information

A Randomized Phase III Trial to Test the Strategy of Changing Therapy Versus Maintaining Therapy for Metastatic Breast Cancer Patients Who Have Elevated Circulating Tumor Cell Levels at First Follow-Up Assessment

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 CellSearch™ 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.