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.
Alaska
	Anchorage
	Alaska Regional Hospital Cancer Center
		Saul Rivkin, MD	Ph:  206-386-2441
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
Arkansas
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Glendale
	Glendale Memorial Hospital Comprehensive Cancer Center
		Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center	Ph:  818-409-7653
	Greenbrae
	California Cancer Care, Incorporated - Greenbrae
		Peter Eisenberg, MD	Ph:  415-925-5000
	Loma Linda
	Loma Linda University Cancer Institute at Loma Linda University Medical Center
		Clinical Trials Office - Loma Linda University Cancer Institute	Ph:  909-558-3375
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Mountain View
	Camino Medical Group - Treatment Center
		Peter Yu, MD	Ph:  408-524-5814
	Palo Alto
	Palo Alto Medical Foundation
		David Leibowitz	Ph:  650-321-4121
	Rancho Mirage
	Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center
		Luke Dreisbach	Ph:  760-674-3600
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	San Francisco
	San Francisco General Hospital Medical Center
		Judith Luce, MD	Ph:  415-476-4082ext.414
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Denver
	Veterans Affairs Medical Center - Denver
		Anthony Elias, MD	Ph:  720-848-1622
	Edwards
	Shaw Regional Cancer Center
		Anthony Elias, MD	Ph:  720-848-1622
Florida
	Lakeland
	Lakeland Regional Cancer Center at Lakeland Regional Medical Center
		James Jakub	Ph:  863-904-1900
Hawaii
	Aiea
	Kapiolani Medical Center at Pali Momi
		Jonathan Cho	Ph:  808-486-6000
	Honolulu
	Cancer Research Center of Hawaii
		Clinical Trials Office - Cancer Research Center of Hawaii	Ph:  808-586-2979
	Hawaii Medical Center - East
		Jonathan Cho	Ph:  808-547-6011
	Kapiolani Medical Center for Women and Children
		Jonathan Cho	Ph:  808-973-8511
	OnCare Hawaii, Incorporated - Kuakini
		Jonathan Cho	Ph:  808-531-8521
	OnCare Hawaii, Incorporated - Lusitana
		Jonathan Cho	Ph:  808-524-6115
	Queen's Cancer Institute at Queen's Medical Center
		Jonathan Cho	Ph:  808-545-8778 800-547-4742
	Straub Clinic and Hospital, Incorporated
		Jonathan Cho	Ph:  808-522-4000 800-232-9491
	Wailuku
	Pacific Cancer Institute - Maui
		Jonathan Cho	Ph:  808-242-2600
Idaho
	Coeur d'Alene
	Kootenai Cancer Center - Coeur d'Alene
		Clinical Trials Office - North Idaho Cancer Center	Ph:  208-666-3764
Illinois
	Alton
	Saint Anthony's Hospital at Saint Anthony's Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Bloomington
	St. Joseph Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Canton
	Graham Hospital
		John Kugler, MD	Ph:  309-243-3605
	Carthage
	Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Chicago
	Creticos Cancer Center at Advocate Illinois Masonic Medical Center
		Clinical Trials Office - Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Ph:  773-296-5360
	Decatur
	Decatur Memorial Hospital Cancer Care Institute
		Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute	Ph:  217-876-6601
	Elmhurst
	Elmhurst Memorial Hospital
		Gerald Kozuh, MD	Ph:  630-614-4060
	Eureka
	Eureka Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Galesburg
	Galesburg Clinic, PC
		John Kugler, MD	Ph:  309-243-3605
	Galesburg Cottage Hospital
		John Kugler, MD	Ph:  309-243-3605
	Harvey
	Ingalls Cancer Care Center at Ingalls Memorial Hospital
		Clinical Trials Office - Ingalls Cancer Care Center at Ingalls Memorial Hospital	Ph:  708-915-6747
	Havana
	Mason District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Hopedale
	Hopedale Medical Complex
		John Kugler, MD	Ph:  309-243-3605
	Macomb
	McDonough District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Mt. Vernon
	Good Samaritan Regional Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Normal
	BroMenn Regional Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Community Cancer Center
		John Kugler, MD	Ph:  309-243-3605
	Mid-Illinois Hematology-Oncology Associates at Community Cancer Center
		John Migas, MD	Ph:  309-451-2207
	Ottawa
	Community Hospital of Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Oncology Hematology Associates of Central Illinois, PC - Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Pekin
	Cancer Treatment Center at Pekin Hospital
		John Kugler, MD	Ph:  309-243-3605
	Peoria
	CCOP - Illinois Oncology Research Association
		John Kugler, MD	Ph:  309-243-3605
	Methodist Medical Center of Illinois
		Clinical Trials Office - Methodist Medical Center of Illinois	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Peoria
		John Kugler, MD	Ph:  309-243-3605
	OSF St. Francis Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Proctor Hospital
		John Kugler, MD	Ph:  309-243-3605
	Peru
	Illinois Valley Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Princeton
	Perry Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Spring Valley
	St. Margaret's Hospital
		John Kugler, MD	Ph:  309-243-3605
	Springfield
	Regional Cancer Center at Memorial Medical Center
		Clinical Trials Office - Regional Cancer Center at Memorial Medical Center	Ph:  217-788-4233
Indiana
	Elkhart
	Elkhart General Hospital
		Rafat Ansari, MD, FACP	Ph:  574-234-5123
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Nattam, MD	Ph:  260-484-8830
	Indianapolis
	St. Vincent Indianapolis Hospital
		Clinical Trials Office - St. Vincent Indianapolis Hospital	Ph:  317-338-2194
	Kokomo
	Howard Community Hospital
		Rafat Ansari, MD, FACP	Ph:  574-234-5123
	La Porte
	Center for Cancer Therapy at LaPorte Hospital and Health Services
		Rafat Ansari, MD, FACP	Ph:  574-234-5123
	South Bend
	CCOP - Northern Indiana CR Consortium
		Rafat Ansari, MD, FACP	Ph:  574-234-5123
	Memorial Hospital of South Bend
		Clinical Trials Office - Memorial Hospital of South Bend	Ph:  800-284-7370
	Saint Joseph Regional Medical Center
		Rafat Ansari, MD, FACP	Ph:  574-234-5123
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Des Moines
	CCOP - Iowa Oncology Research Association
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	John Stoddard Cancer Center at Iowa Lutheran Hospital
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Lutheran Hospital	Ph:  515-241-8704
	John Stoddard Cancer Center at Iowa Methodist Medical Center
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Methodist Medical Center	Ph:  515-241-6727
	Medical Oncology and Hematology Associates at John Stoddard Cancer Center
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Medical Oncology and Hematology Associates at Mercy Cancer Center
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Mercy Cancer Center at Mercy Medical Center - Des Moines
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Mercy Capitol Hospital
		Roscoe Morton, MD, FACP	Ph:  515-282-2921
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-0088
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Waterloo
	Cedar Valley Medical Specialists, PC - West Ridgeway Avenue
		Boriana Kamenova	Ph:  319-833-5907
	Covenant Cancer Treatment Center
		Clinical Trials Office - Covenant Cancer Treatment Center	Ph:  319-272-2070
Kansas
	Chanute
	Cancer Center of Kansas, PA - Chanute
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Dodge City
	Cancer Center of Kansas, PA - Dodge City
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	El Dorado
	Cancer Center of Kansas, PA - El Dorado
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Independence
	Cancer Center of Kansas-Independence
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Kingman
	Cancer Center of Kansas, PA - Kingman
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Lawrence
	Lawrence Memorial Hospital
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Liberal
	Southwest Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Newton
	Cancer Center of Kansas, PA - Newton
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Parsons
	Cancer Center of Kansas, PA - Parsons
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Pratt
	Cancer Center of Kansas, PA - Pratt
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Salina