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.
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.
Brief Title
S0500 Treatment Decision Making Based on Blood Levels of Tumor Cells for Metastatic Breast Cancer Treated With Chemo
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Eligibility 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
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
* 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
Inclusion 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
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
* 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
Gender
Female
Gender Based
false
Keywords
recurrent breast cancer
stage IV breast cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT00382018
Org Class
Network
Org Full Name
SWOG Cancer Research Network
Org Study Id
CDR0000504319
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Overall Survival
Outcome Time Frame
Every 3 months until progression then every 6 months for 5 years or until death
Outcome Description
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
Outcome Measure
Progression-free Survival
Outcome 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.
Outcome Description
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.
Outcome Measure
Progression Free Survival
Outcome Time Frame
every 3 months until progression
Secondary Ids
Secondary Id
S0500
Secondary Id
U10CA032102
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Toxicity assessment was evaluated after 3 weeks, 6 weeks, and every 6 weeks thereafter until progression
Outcome Measure
Number of Patients With Adverse Events That Are Related to Study Drugs
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404