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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00382018
Recruitment Status : Completed
First Posted : September 28, 2006
Results First Posted : April 4, 2017
Last Update Posted : November 6, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE September 26, 2006
First Posted Date  ICMJE September 28, 2006
Results First Submitted Date  ICMJE December 16, 2016
Results First Posted Date  ICMJE April 4, 2017
Last Update Posted Date November 6, 2017
Study Start Date  ICMJE October 2006
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2017)
  • Overall Survival [ Time Frame: Every 3 months until progression then every 6 months for 5 years or until death ]
    From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
  • Progression-free Survival [ Time Frame: every 3 months until progression. From date of registration to date of first documentation of progressive disease, death due to any cause or symptomatic deterioration, whichever occurs first, assessed up to five years. ]
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
  • Progression Free Survival [ Time Frame: every 3 months until progression ]
    From date of registration to date of first documentation of progressive disease, death due to any cause or symptomatic deterioration, whichever occurs first. Patients last known to be alive and progression-free are censored at date of last contact.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2017)
Number of Patients With Adverse Events That Are Related to Study Drugs [ Time Frame: Toxicity assessment was evaluated after 3 weeks, 6 weeks, and every 6 weeks thereafter until progression ]
Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: February 15, 2017)
Correlation of CTC Levels With Breast Cancer Tumor Markers [ Time Frame: Baseline, Weeks 4, 8, 13, 25, 37 and at progression ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE S0500 Treatment Decision Making Based on Blood Levels of Tumor Cells for Metastatic Breast Cancer Treated With Chemo
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: chemotherapy
No administration details available
Study Arms  ICMJE
  • Active Comparator: Group 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.
    Intervention: Drug: chemotherapy
  • Experimental: Group 2
    Patients continue to receive their current chemotherapy regimen without change.
    Intervention: Drug: chemotherapy
  • Active Comparator: Group 3, Arm I
    Patients continue with their current chemotherapy regimen without change.
    Intervention: Drug: chemotherapy
  • Experimental: Group 3, Arm II
    Patients switch to a different chemotherapy regimen. Selection of a new chemotherapy regimen is made by the patient's doctor.
    Intervention: Drug: chemotherapy
Publications * Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O'Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol. 2014 Nov 1;32(31):3483-9. doi: 10.1200/JCO.2014.56.2561. Epub 2014 Jun 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 15, 2017)
624
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 11, 2017
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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

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 metastatic 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT00382018
Other Study ID Numbers  ICMJE CDR0000504319
S0500 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Cancer and Leukemia Group B
Investigators  ICMJE
Study Chair: Jeffrey B. Smerage, MD, PhD University of Michigan Rogel Cancer Center
Study Chair: Daniel F. Hayes, MD University of Michigan Rogel Cancer Center
Study Chair: Eric P. Winer, MD Dana-Farber Cancer Institute
PRS Account Southwest Oncology Group
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP