Clinical trial NCT00274768: Capecitabine in Treating Patients With Metastatic Breast Cancer
Official title: Phase II Study of Fixed-Dose Capecitabine in Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
male breast cancer
recurrent breast cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-11
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Response Rate
timeFrame: Participants were followed to progression, evaluated every 12 weeks
Secondary outcomes:
measure: Clinical Benefit as Assessed by Lack of Progression for at Least 24 Weeks
timeFrame: 3-week cycles of treatment up to 16 cycles
measure: Pharmacokinetics of Capecitabine and Metabolites as Assessed by Maximum Plasma Concentration
timeFrame: 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours
measure: Pharmacokinetics of Capecitabine and Metabolites as Assessed by Area Under the Curve (AUC)
timeFrame: 0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours
measure: Adherence and Compliance to Oral Medication Using Electronic Monitoring
timeFrame: 3-week cycles of treatment up to 16 cycles
measure: Time to Treatment Failure
timeFrame: 3-week cycles of treatment up to 16 cycles
Other outcomes:
Locations:
city: Annapolis
country: United States
facility: DeCesaris Cancer Institute at Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Antonio C. Wolff, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fackler MJ, Lopez Bujanda Z, Umbricht C, Teo WW, Cho S, Zhang Z, Visvanathan K, Jeter S, Argani P, Wang C, Lyman JP, de Brot M, Ingle JN, Boughey J, McGuire K, King TA, Carey LA, Cope L, Wolff AC, Sukumar S. Novel methylated biomarkers and a robust assay to detect circulating tumor DNA in metastatic breast cancer. Cancer Res. 2014 Apr 15;74(8):2160-70. doi: 10.1158/0008-5472.CAN-13-3392.