Breast Cancer
Conditions
Keywords
stage IV breast cancer, male breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well capecitabine works in treating patients with metastatic breast cancer.
Detailed description
OBJECTIVES: Primary * Determine the response rate in patients with metastatic breast cancer treated with a fixed-dose of capecitabine. Secondary * Determine the clinical benefit, time to treatment failure (TTF), safety, and toxicity profile of this regimen in these patients. * Determine the pharmacokinetics (PK) and pharmacogenetics in these patients. * Correlate pharmacodynamic effects of this drug with toxicity and response in these patients. * Determine compliance and adherence to this regimen and correlate with PK parameters in these patients. OUTLINE: This is an open-label study. Patients receive a fixed-dose of oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Interventions
DRUGcapecitabine
A total of 115 cycles of therapy were administered and five patients did not complete cycle 1. The median number of cycles initiated was four (range 1-16).
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed diagnosis of adenocarcinoma of the breast * Evidence of metastatic involvement (stage IV disease) * Patients must have measurable disease * At least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) * Treated brain metastases (surgery or radiation therapy) allowed if clinically stable * Patients with leptomeningeal disease are ineligible * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Male or female * Menopausal status not specified * Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Creatinine clearance \> 50 mL/min * Fertile patients must use effective contraception * No history of another severe and/or life-threatening medical disease * No other active primary malignancy * Not pregnant or nursing * Negative pregnancy test * Patients with asymptomatic HIV infection are eligible * Liver dysfunction score ≤ 9 * No pre-existing liver disease (i.e., cirrhosis or active viral hepatitis) * No active gastrointestinal malabsorption illness * No clinically significant cardiac disease, including the following: * Congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmias not well controlled with medication, or myocardial infarction within the past six months * No prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to fluorouracil, or known dihydropyrimidine dehydrogenase deficiency * No history of uncontrolled seizures or central nervous system disorders * No significant history of noncompliance to medical regimens * No clinically significant psychiatric disability that would preclude study compliance PRIOR CONCURRENT THERAPY: * No previous capecitabine * Up to 3 prior cytotoxic regimens allowed for metastatic disease * Prior noncytotoxic therapy allowed (e.g., hormonal treatment or trastuzumab) * No other concurrent therapies intended to treat the primary condition including chemotherapy, biologic agents, or immunotherapy * No concurrent anti-estrogen therapy, radiation therapy, or investigational systemic therapy * No other concurrent investigational drugs * No concurrent use of the following drugs: warfarin for full anticoagulation, cimetidine, or azidothymidine (AZT) * Mini-dose warfarin for prophylaxis of central venous catheter thrombosis allowed * At least 4 weeks since prior sorivudine or brivudine * Concurrent use of bisphosphonates allowed if initiated before beginning study therapy * Concurrent use of megestrol acetate suspension as an appetite stimulant allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Participants were followed to progression, evaluated every 12 weeks | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit as Assessed by Lack of Progression for at Least 24 Weeks | 3-week cycles of treatment up to 16 cycles | The overall clinical benefit rate as assessed by number of participants with lack of progression for at least 24 weeks. |
| Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration | 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours | Pharmacokinetics of Capecitabine and metabolites \[5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-fluorouracil (FU)\] assessed using maximum plasma concentration (Cmax) in ng/mL. |
| Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) | 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours | Pharmacokinetics of Capecitabine and metabolites \[5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-FU\] assessed using AUC in ng\*h/mL. |
| Adherence and Compliance to Oral Medication Using Electronic Monitoring | 3-week cycles of treatment up to 16 cycles | This was assessed by number of participants who did not miss any doses of Capecitabine during treatment using the Medication Event Monitoring System (MEMS). |
| Time to Treatment Failure | 3-week cycles of treatment up to 16 cycles | Time to treatment failure in weeks |
Countries
United States
Participant flow
Recruitment details
Thirty patients with metastatic breast cancer were consented between August 2005 and December 2008. Twenty six patients were eligible and initiated treatment on-study.
Pre-assignment details
Women (≥ 18 or older) with a histologically confirmed metastatic (stage 4) adenocarcinoma of the breast were eligible. Several inclusion and exclusion applied to confirm that women were appropriate to take part in the study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine The starting dose of capecitabine was 3,000 mg (total daily dose) given in two divided daily doses for 14 days followed by 7 days of rest (1 cycle = 21 days). Missed doses were not substituted. Treatment was continued until unacceptable toxicity, disease progression, or withdrawal of consent. | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Capecitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 26 |
| other Total, other adverse events | 20 / 26 |
| serious Total, serious adverse events | 2 / 26 |
Outcome results
Primary
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Participants were followed to progression, evaluated every 12 weeks
Population: Any participant who completed at least one (1) cycle of capecitabine administration was evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine | Response Rate | 21 participants |
Secondary
Adherence and Compliance to Oral Medication Using Electronic Monitoring
This was assessed by number of participants who did not miss any doses of Capecitabine during treatment using the Medication Event Monitoring System (MEMS).
Time frame: 3-week cycles of treatment up to 16 cycles
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Capecitabine | Adherence and Compliance to Oral Medication Using Electronic Monitoring | 13 Participants |
Secondary
Clinical Benefit as Assessed by Lack of Progression for at Least 24 Weeks
The overall clinical benefit rate as assessed by number of participants with lack of progression for at least 24 weeks.
Time frame: 3-week cycles of treatment up to 16 cycles
Population: Five patients did not complete cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Capecitabine | Clinical Benefit as Assessed by Lack of Progression for at Least 24 Weeks | 4 Participants |
Secondary
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC)
Pharmacokinetics of Capecitabine and metabolites \[5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-FU\] assessed using AUC in ng\*h/mL.
Time frame: 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) | Capecitabine | 7255 ng*h/mL | Standard Deviation 4180 |
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) | 5'-DFCR | 11344 ng*h/mL | Standard Deviation 5583 |
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) | 5'-DFUR | 6653 ng*h/mL | Standard Deviation 2166 |
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC) | 5-FU | 1230 ng*h/mL | Standard Deviation 1826 |
Secondary
Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration
Pharmacokinetics of Capecitabine and metabolites \[5-fluoro-5'-deoxycytidine (5'-DFCR), 5-fluoro-5'-dexoxyuridine (5'-DFUR), and 5-fluorouracil (FU)\] assessed using maximum plasma concentration (Cmax) in ng/mL.
Time frame: 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration | Capecitabine | 9324 ng/mL | Standard Deviation 7015 |
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration | 5'-DFCR | 6353 ng/mL | Standard Deviation 2590 |
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration | 5'-DFUR | 4597 ng/mL | Standard Deviation 2608 |
| Capecitabine | Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration | 5-FU | 753 ng/mL | Standard Deviation 1209 |
Secondary
Time to Treatment Failure
Time to treatment failure in weeks
Time frame: 3-week cycles of treatment up to 16 cycles
Population: Five patients did not complete cycle 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine | Time to Treatment Failure | 12 weeks |