Capecitabine in Treating Patients With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase II Study of Fixed-Dose Capecitabine in Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00274768
• Other study ID #: J0425 CDR0000446286
• Secondary ID: P30CA006973JHOC-
• Status: Completed
• Phase: Phase 2
• Start date: April 2004
• Est. completion date: November 2012

Study information

• Verified date: January 2020
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: November 2012
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• capecitabine
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).

Locations

Country	Name	City	State
United States	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Participants were followed to progression, evaluated every 12 weeks
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.	3-week cycles of treatment up to 16 cycles
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.	0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours
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.	0.25, 0.5, 1, 2, 3, 4, 5, 6 and 8 hours
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).	3-week cycles of treatment up to 16 cycles
Secondary	Time to Treatment Failure	Time to treatment failure in weeks	3-week cycles of treatment up to 16 cycles