Conditions: Breast Cancer
Keywords: recurrent breast cancer stage IV breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 624
Healthy volunteers: no

Brief summary:
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Measuring blood levels of tumor cells may help in learning how well chemotherapy works to kill metastatic breast cancer cells and allow doctors to plan better treatment. When blood levels of tumor cells are high while receiving chemotherapy, it is not yet known whether it is more effective to change chemotherapy regimens at that time or wait until disease progression.

PURPOSE: This randomized phase III trial is studying treatment decision making based on blood levels of tumor cells in women with metastatic breast cancer receiving chemotherapy.

Detailed description:
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.

Arms:
arm 1: 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. arm 2: Patients continue to receive their current chemotherapy regimen without change. arm 3: Patients continue with their current chemotherapy regimen without change. arm 4: Patients switch to a different chemotherapy regimen. Selection of a new chemotherapy regimen is made by the patient's doctor.

Interventions: intervention 1: chemotherapy
Intervention descriptions: intervention 1: No administration details available

Protocol document: