Capecitabine in Treating Patients With Metastatic Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: capecitabine

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • DeCesaris Cancer Institute at Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capecitabine; 26 patients received the pre-defined starting dose of capecitabine of 3,000 mg orally daily given in two divided doses. Two thirds of the patients received either the same dose or a 500 mg lower dose compared to what would have been administered with a commonly used body surface area (BSA)-dosing schedule (2,000 mg/m2 with rounding down to nearest 500 mg multiple).	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).; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Time to Treatment Failure	Time to treatment failure in weeks	3-week cycles of treatment up to 16 cycles

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Antonio C. Wolff, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

General Publications

• 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. Erratum In: Cancer Res. 2014 Jun 1;74(11):3196.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (Estimate): January 11, 2006

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; male breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: J0425 CDR0000446286; P30CA006973 (U.S. NIH Grant/Contract); JHOC-J0425 (Other Identifier: SKCCC); JHOC-SKCCC-J0425 (Other Identifier: SKCCC); JHOC-IRB-04032502 (Other Identifier: SKCCC)