Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Treatment Decision Making Based on Blood Levels of Tumor Cells in Women With Metastatic Breast Cancer Receiving Chemotherapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Diagnostic, Treatment	Active	Not specified	NCI	SWOG-S0500 S0500, CALGB-SWOG-S0500, NCT00382018

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. 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.
2. 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.
3. 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.
4. Determine the prognostic value of sequentially collected CTC values in these patients.
5. Compare toxicity between patients with and without elevated CTCs after 3 weeks of first-line chemotherapy AND between the two randomized treatment arms.

Secondary

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

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer
  • Clinical evidence of metastatic disease (stage IV disease)
  • Newly metastatic disease OR progressive metastatic disease while on hormonal therapy
• Meets 1 of the following criteria:
  • Measurable disease
  • Bone-only disease*

   [Note: *Patients with nonmeasurable disease that does not include bone are not eligible]

• HER-2 status determined by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) assay
  • HER-2 positivity is defined as IHC 3+ or FISH+
  • If IHC is indeterminate (2+), FISH must be performed to classify disease
• Planning to undergo first-line chemotherapy for metastatic disease
• Patients with brain metastases must have stable disease for > 90 days after completion of prior radiotherapy to the brain
• No leptomeningeal disease
• Hormone receptor status not specified

Prior/Concurrent Therapy:

• See Disease Characteristics
• Prior hormonal therapy, bisphosphonate therapy, trastuzumab (Herceptin®), and/or bevacizumab for metastatic disease allowed
  • Any number of exogenous hormonal therapies for metatstatic disease and/or as adjuvant therapy allowed
• At least 1 year since prior adjuvant chemotherapy
• At least 2 weeks since prior minor surgery and recovered
• At least 4 weeks since prior major surgery and recovered
• No prior chemotherapy for metastatic disease
• Concurrent hormonal therapy and/or bisphosphonate therapy allowed
• Concurrent trastuzumab and/or bevacizumab allowed

Patient Characteristics:

• Female
• Menopausal status not specified
• Zubrod performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

Expected Enrollment

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

Outcomes

Overall survival
Progression-free survival
Prognostic value of sequentially collected circulating tumor cell (CTC) values
Toxicity

Correlation of CTC levels with breast cancer tumor markers

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Jeffrey Smerage, MD, PhD, Study coordinator		Ph: 734-936-0453; 800-865-1125 Email: smerage@umich.edu
Daniel Hayes, MD, Study coordinator		Ph: 734-615-6725; 800-865-1125 Email: hayesdf@umich.edu

Cancer and Leukemia Group B

Eric Winer, MD, Study coordinator		Ph: 617-632-3800; 866-790-4500

U.S.A.
Michigan
	Lambertville
	Haematology-Oncology Associates of Ohio and Michigan, PC
		Paul Schaefer, MD	Ph:  419-479-5605
Ohio
	Bowling Green
	Wood County Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Maumee
	Northwest Ohio Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
		Paul Schaefer, MD	Ph:  419-479-5605
	St. Luke's Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Oregon
	St. Charles Mercy Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Clinic - Oregon
		Paul Schaefer, MD	Ph:  419-479-5605
	Sylvania
	Flower Hospital Cancer Center
		Clinical Trials Office - Flower Hospital Cancer Center	Ph:  419-824-1842
	Toledo
	CCOP - Toledo Community Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Medical University of Ohio Cancer Center
		Clinical Trials Office - Medical University of Ohio Cancer Center	Ph:  419-383-6583
	St. Anne Mercy Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	St. Vincent Mercy Medical Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Clinic, Incorporated - Main Clinic
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Hospital
		Clinical Trials Office - Toledo Hospital	Ph:  419-824-1842

See All Trial Sites

Related Information

Featured trial article

Registry Information
Official Title		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
Trial Start Date		2006-10-01
Trial Completion Date		2011-09-15 (estimated)
Registered in ClinicalTrials.gov		NCT00382018
Date Submitted to PDQ		2006-08-15
Information Last Verified		2010-02-05
NCI Grant/Contract Number		CA32102

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