Clinical Trial Result Information

Protocol number
M66106

Title of Study
A Phase 2 study on the use of capecitabine in patients ≥65 years with advanced breast cancer

Sponsor
Roche S.p.A

Company division
Pharmaceutical

Product name
Xeloda

Generic name
capecitabine

Therapeutic area
Breast Cancer

Clinical study summary
This open-label, non-comparative, single-center study evaluated the efficacy and safety of 2 doses (1000mg/m2 twice daily (bid) and 1250mg/m2 (bid)) oral Xeloda in elderly patients with advanced or metastatic breast cancer. Patients were divided into 2 sub-groups based on treatment dose.

Study center(s)
1 in Italy.

Phase of development
II

Objectives
Primary: To evaluate the safety and feasibility of Xeloda in elderly patients untreated or pretreated for metastatic disease with hormonal therapy and/or chemotherapy.
Secondary: To determine antitumor activity in terms of response rate and time to progression.

Methodology
After screening, patients were assigned to one of the 2 treatment groups. They received treatment in 3 week cycles, with Xeloda being taken twice daily from days 1-14. hematology measurements were made after each cycle, and blood chemistry measurements and tumor evaluations were made after every second cycle.

Number of patients (planned/analyzed)
71 planned, 73 enrolled.

Diagnosis and main criteria for inclusion
Elderly patients with untreated advanced or metastatic breast cancer or locally advanced or metastatic breast cancer recurrent after hormonal therapy (≤2 lines) and/or chemotherapy (1 line) for metastatic disease.

Test product, dose and mode of administration or test procedure
Xeloda 1250 or 1000 mg/m2/bid po., administered bid. after meals on Days 1–14 in 3-week cycles.

Duration of treatment
3 week cycles: continuation of treatment relied on tumor re-assessment.

Reference therapy, dose and mode of administration or reference procedure
Not applicable

Criteria for evaluation (efficacy, safety)
Efficacy parameters: complete remission; partial remission; stable disease (SD); progressive disease; time to disease progression (TTP). Safety parameters: Adverse events (AEs) and laboratory test abnormalities.

Statistical methods
Efficacy: The overall response achieved within the time from randomization to progressive disease or end of study was reported. Patients with no tumor assessment after baseline were classified as non-responders. TTP was computed as the time between treatment start and the date of disease progression or death, or the last date the patient was known to be progression-free. For the analysis of survival, the time between treatment start and the date of death or the last date the patient was known to be alive was computed. Analyses of response and duration of response were based on all responding patients. Time to response was computed as the time between treatment start and the date when the patient was first classified as having a complete or partial response.

Safety: A standard safety analysis was performed reporting AEs in frequency tables and laboratory parameters in shift tables. Times to first onset of specific types of AEs were summarized in plots of the Kaplan-Meyer estimates.

Summary (efficacy, safety, other results)
Efficacy – All patients who entered the study were included in the efficacy analysis. The population analyzed was split into 2 subgroups based on treatment dose.

Forty-three patients received Xeloda 1000 mg/m2/bid. Sixteen patients showed complete (2.3%) or partial response (34.8%) to treatment. The duration of response ranged from 57 to 181 days, and the time to response ranged from 20 to 163 days. Ten patients showed SD, whereas 4 patients reported progression of disease as best overall response. Eight patients reported disease progression. The time to disease progression ranged from 1 to 192 days, and the time of survival showed the same minimum and maximum values. Only 1 patient (2.33%) had a dose reduction during study.

Thirty patients were treated with Xeloda 1250 mg/m2/bid. Thirteen patients showed complete (3.3%) or partial response (40.3%) to treatment. The duration of response ranged from 103 to 176 days, and the time to response ranged from 20 to 65 days. Twenty-one patients showed stable disease, whereas 3 patients reported progression of disease as best overall response. Fourteen patients reported disease progression. One patient died due to progression of disease. The time to disease progression ranged from 13 to 176 days, and the time of survival showed the same minimum and maximum values. Nine patients had dose modification during the study.

The difference between the results of 1000 mg/m2/bid treatment or 1250 mg/m2/bid treatment with Xeloda was analyzed. No significant differences were found for either response or progression endpoints.

Safety – The safety population analyzed (73 patients) was split in 2 subgroups based on treatment dosage.

The 43 patients treated with Xeloda 1000 mg/m2/bid reported a total of 233 AEs, mainly asthenia (19.3%) and hand-foot syndrome (18.4%);72.5% of AEs were considered related to treatment. Toxicity was mainly Grade 1(46.8%) and Grade 2 (39.1%), with 8 AEs (3.4%) being classified as severe. Twenty-six AEs (11.2%) resolved after dose reduction or after stopping treatment. Three patients discontinued treatment due to acute myocardial infarction, heart failure and grade 4 diarrhea, respectively. In addition, one patient died of heart failure, possibly due to study drug.

The 30 patients treated with Xeloda 1250 mg/m2/bid reported a total of 155 AEs, mainly hand-foot syndrome (25.8%) and nausea (14.8%);74.2% of AEs were considered related to treatment. Toxicity was mainly Grade 1 (55.5%) and Grade 2 (31.6%), with 15 AEs (9.7%)being classified as severe. Thirty-three AEs (21.3%) resolved after dose reduction or after stopping treatment. Two patients discontinued treatment due to grade 3 diarrhea, and deterioration of general condition (considered related to study drug), respectively. In addition, 2 patients died due to grade 4 diarrhea and severe dehydration.

The most common significant changes in laboratory values were thrombocytopenia and neutropenia, related to treatment with Xeloda.

Conclusions
The results of this clinical study in older patients with advanced or metastatic breast cancer demonstrate that treatment with Xeloda induced complete or partial responses in 43.3% patients, with a time to response of 51 ± 36 days and a duration of response of 133 ± 25 days. Xeloda was better tolerated at the 1000 mg/m2/bid dosage than at the 1250 mg/m2/bid dosage. Only 3.4% of AEs were reported as severe for treatment with Xeloda 1000 mg/m2/bid, whereas 9.7% of AEs were reported as severe for Xeloda 1250 mg/m2/bid.

Publications (references, if available)
Bajetta E, Procopio G, Celio L et al. Safety and Efficacy of Two Different Doses of Capecitabine in the Treatment of Advanced Breast Cancer in Older Women. J. Clin. Oncology 2005; 23 (10): 1-7

Date of report
4/23/2003