Standard Versus Continuous Capecitabine in Advanced Breast Cancer

Phase 2

Completed

Conditions: Metastatic Breast Cancer

Interventions: Drug: Capecitabine

Registration Number: NCT00418028

Lead Sponsor: Hospital San Carlos, Madrid

Brief Summary: Capecitabine is active in metastatic breast cancer but the conventional schedule (1250 mg/m2/12 hr 2 weeks on, one week off) produces grade 2 or greater hand and foot syndrome in up to 50% of patients leading to those reductions. There are theoretical reasons to administer S-phase specific agents in continuous, protracted rather than intermittent schedules. The investigators study compares the standard schedule (1250 mg/m2/12 hr 2 weeks on, one week off) with a continuous administration schedule (800 mg/m2/12hr). The latter administer approximately the same cumulative dose of capecitabine as the standard schedule. The study hypothesis is that grade 2 or greater hand and foot syndrome will be reduced from 50% (standard arm) to 20% (experimental arm). The investigators assume similar antitumor activity in both arms.

Detailed Description: Capecitabine is active in metastatic breast cancer but the conventional schedule (1250 mg/m2/12 hr 2 weeks on, one week off) produces grade 2 or greater hand and foot syndrome in up to 50% of patients leading to those reductions. Some authors have tested continuous administration schedules of capecitabine, showing better tolerance and apparently similar antitumor activity. Capecitabine is a pro-drug of 5-FU and mimics an i.v. continuous infusion administration of this antimetabolite. On the other hand, there are theoretical reasons to administer S-phase specific agents in continuous, protracted rather than intermittent schedules. Our study compares the standard schedule(1250 mg/m2/12 hr 2 weeks on, one week off)with a continuous administration schule (800 mg/m2/12hr). The latter schedule administer approximately the same cumulative dose of capecitabine as the standard one. The study hypothesis is that grade 2 or greater hand and foot syndrome will be reduced from 50% (standard arm) to 20% (experimental arm). The investigators assume similar antitumor activity in both arms.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 195

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A Cint	Capecitabine	Capecitabine will be administered orally at a dose of 1250 mg/m2 twice-daily (in the morning and in the evening, the equivalent of a total daily dose of 2500 mg/m2) for 14 days, in 3 week cycles with a resting period of 7 days,until disease progression or severe toxicity. Dose adjustments were made in patients with grade 3 or greater diarrhea or hand and food syndrome.
B Ccont	Capecitabine	Capecitabine 800 mg/m2 orally twice-daily (in the morning and in the evening the equivalent of one dose of 1600 mg/m2) for 21 days, in 3 week cycles without resting period, until disease progression or severe toxicity. Dose adjustments were made in patients with grade 3 or greater diarrhea or hand and food syndrome.

Primary Outcome Measures

Name	Time	Method
Time to Progression	After 1 year from the treatment start day.	Time to Progression (TTP) is defined as the time (in months) from the moment the patient starts the study treatment to the date of progressive disease. That is, a patient has an event is she progresses or dies due to progressive disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).

Secondary Outcome Measures

Name	Time	Method
Response Rate	Through the study treatment, an average of 5 months.	Response was evaluated using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), every 3 cycles of chemotherapy (each cycle lasts 3 weeks) and at the end of treatment (at 21 weeks from the start of treatment).
Overall Survival	Time to survival is the number of months from the study treatment start date to the date of death, assessed up to 100 months.	An event is defined as death. A patient is censored if she does not die. The censoring date is last contact date.
Clinical Benefit	Months from "CR","PR" or "SD" (the first one) until Progression date, new treatment or last contact date.	A patient experiences a Clinical Benefit if the following is satisfied: Criterion: The patient has "Complete response", "Partial Response" or "Stable Disease" and it continues during more than 3 months.
Progression Free Survival	Time (in months) from the moment the patient starts the study treatment to the date of progressive disease assessed up to 84 months.	Progression Free Survival is defined as the time (in months) from the moment the patient starts the study treatment to the date of progressive disease. That is, a patient has an event is she progresses or dies for any reason.
Response Duration	Time from the moment the Partial or Complete Response is reported to the date the patient Progresses or Dies, whichever happens first, assessed up to 72 weeks.	Response duration is computed for all patients with Partial Response or Complete Response, during the treatment period, as the time from the moment the Partial or Complete Response is reported to the date the patient Progresses or Dies, whichever happens first. A patient is censored if she does not progress or die. In these cases Response duration is computed as the time from the moment the Partial or Complete Response is reported to the last contact date.
Time to Treatment Failure	Time (in months) from the moment the patient starts the study treatment to the end of treatment date (due to death, progressive disease, adverse events, patient's decision or investigator criteria, assessed up to 72 months.	Time to treatment failure (TTF) is defined as the time (in months) from the moment the patient starts the study treatment to the end of treatment date (due to death, progressive disease, adverse events, patient's decision or investigator criteria. If a patient did not end the treatment, it is censored. The censoring date is the date of the last dose received.