Standard Versus Continuous Capecitabine in Advanced Breast Cancer

San Carlos Clinical Hospital

Status and phase: Completed; Phase 3; Phase 2

Conditions: Metastatic Breast Cancer

Treatments: Drug: Capecitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT00418028

05/237

2004-002759-15 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 195 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Patients diagnosed with metastatic breast cancer
2. Patients that either have received previous treatment with anthracyclines and/or taxanes or not (either as advance or in metastatic disease).
3. The patient is ambulatory with a functional ECOG < 2 status (see Appendix 2).
4. Patient presents, at least one lesion measurable according to RECIST criteria (see Appendix 3)
5. Patients with a life expectancy of at least 3 months.
6. Patients that agree to and are able to fulfill the requirements of the whole protocol through the whole study.

Exclusion criteria:

1. Patients that have previously shown unexpected severe reactions to therapy with fluoropyrimidines or with a known sensitivity to 5-fluorouracile.

2. Patients previously treated with capecitabine.

3. Patients with organ transplants.

4. Other diseases or severe affections:

   1. Patients with previous convulsions, central nervous system diseases or psychiatric diseases, including dementia, that the investigator might consider clinically significant and which adversely affect therapeutic compliance.
   2. Patients with severe intellectual impairment, unable to carry out basic daily routines and established depression.
   3. Clinical significant cardiac disease (e. g. . congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not fully controlled with medication) or myocardial infarction within the last 12 months.
   4. Severe renal impairment (baseline creatinine clearance < 30 ml/min)

5. Patients with signs of metastasis in the CNS. Patients with a history of uncontrolled convulsions, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake should be excluded.

6. Patients with an active infection.

7. Patients with a history of other neoplasias during the previous five years, except for basal cell skin cancer or cervical cancer in situ, both cured.

8. Patients showing the following laboratory values:

   1. Neutrophil count < 555 x 109/l
   2. Platelet count< 100 x 109/l
   3. Serum creatinine > 1,5 x upper normality limit
   4. seric bilirubin > 2,0 x upper normality limit
   5. ALAT, ASAT > 2,5 x upper normality limit or > 5 x upper normality limit in case of liver metastases
   6. Alkaline phosphatase > 2,5 x upper normality limit > 5 x upper normality limit in case of liver metastases o > 10 x upper normality limit in case of bone metastases.

9. Patients under radiotherapy four weeks prior to the initiation of the study treatment, or under previous radiotherapy on the marker lesions be measured during the study (new marker lesions that appear in previously irradiated areas are accepted) or patients who are receiving programmed radiotherapy.

10. Patients under major surgery within 4 weeks prior to study treatment or who have not completely recovered from the effects of major surgery.

11. Patients who lack upper gastrointestinal tract physical integrity or with malabsorption syndrome.

12. Patients who have received more than two cycles of chemotherapy for the metastatic disease.

13. Patients Her2 + per FISH ó +++ Immunohistochemistry

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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195 participants in 2 patient groups

A Cint

Active Comparator group

Description:

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.

Treatment:

Drug: Capecitabine

B Ccont

Experimental group

Description:

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.

Treatment:

Drug: Capecitabine