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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>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. | Drug: chemotherapy<br>* No administration details available<br>|
| Experimental: Group 2<br>Patients continue to receive their current chemotherapy regimen without change. | Drug: chemotherapy<br>* No administration details available<br>|
| Active Comparator: Group 3, Arm I<br>Patients continue with their current chemotherapy regimen without change. | Drug: chemotherapy<br>* No administration details available<br>|
| Experimental: Group 3, Arm II<br>Patients switch to a different chemotherapy regimen. Selection of a new chemotherapy regimen is made by the patient's doctor. | Drug: chemotherapy<br>* No administration details available<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | 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. | Every 3 months until progression then every 6 months for 5 years or until death | 
| Progression-free Survival | 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 | 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 Free Survival | 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. | every 3 months until progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events That Are Related to Study Drugs | 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. | Toxicity assessment was evaluated after 3 weeks, 6 weeks, and every 6 weeks thereafter until progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer