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Standard Versus Continuous Capecitabine in Advanced Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Hospital San Carlos, Madrid.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Hospital Juan Canalejo, La Coruña, Spain
Information provided by:
Hospital San Carlos, Madrid
ClinicalTrials.gov Identifier:
NCT00418028
First received: January 3, 2007
Last updated: August 8, 2011
Last verified: March 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
 Drug: drug: capecitabine
Drug: capecitabine
 Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Continuous Versus Standard Capecitabine in Advanced Breast Cancer.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hospital San Carlos, Madrid:

Primary Outcome Measures:
  • time to progression [ Time Frame: 2005-2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: 2005-2011 ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 2005-2011 ] [ Designated as safety issue: Yes ]
  • Relation of patient polymorphisms to toxicity and activity [ Time Frame: 2005-2011 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 196
Study Start Date: September 2005
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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.
 Drug: drug: capecitabine
800 mg/m2 twice a day orally continuous administration until disease progression or severe toxicity. Dose adjustments were made in patients with grade 3 or greater diarrhea or hand and food syndrome.
Other Name: xeloda
Active Comparator: 2
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.
 Drug: capecitabine
1250 mg/m2 twice a day orally x 14 days every 3 weeks until disease progression or severe toxicity. Dose adjustments were made in patients with grade 3 or greater diarrhea or hand and food syndrome.
Other Name: xeloda

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 neoplasies 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 límite superior de normalidad
    4. seric bilirubin > 2,0 x límite superior de normalidad
    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 +++ Inmunohistochemistry
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00418028

Locations
Spain
Hospital Clinico San Carlos
Madrid, Spain, 28040
Sponsors and Collaborators
Hospital San Carlos, Madrid
Hospital Juan Canalejo, La Coruña, Spain
Investigators
Principal Investigator: Miguel Martin, MD,PhD Hospital Clinico San Carlos
Principal Investigator: Noelia Martinez, MD PhD Hospital Ramón y Cajal
Principal Investigator: Ramos Manuel, MD PhD Centro Oncológico Galicia
Principal Investigator: Calvo MD, PhD C.H.U. A Coruña (Hospital Juan Canalejo)
Principal Investigator: Ana Lluch, MD PhD Hospital Clinico Universitario de Valencia
Principal Investigator: Pilar Zamora, MD,PhD Hospital de la Paz
Principal Investigator: Montserrat Muñoz, MD,PhD Hospital Clinic i Provincial
Principal Investigator: Jose Ignacio Chacon, MD,PhD H. Virgen de la Salud
Principal Investigator: Blanca Hernando, MD,PhD Hospital General Yagüe
Principal Investigator: Manuel Ruiz Borrego, MD,PhD Hospital Virgen del Rocio
Principal Investigator: Lucía Heras, MD,PhD H. General Hospitalet
Principal Investigator: Juan de la Haba, MD,PhD Hospital Reina Sofía
Principal Investigator: Constela, MD,PhD Hospital de Pontevedra
  More Information

No publications provided

Responsible Party: Miguel Martin, MD, Hospital Gregorio Marañón
ClinicalTrials.gov Identifier: NCT00418028     History of Changes
Other Study ID Numbers: 05/237
Study First Received: January 3, 2007
Last Updated: August 8, 2011
Health Authority: Spain: Ministry of Health

Keywords provided by Hospital San Carlos, Madrid:
capecitabine
schedule
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013