Metastatic Breast CancerPhase 2/3NCT00418028
Standard Versus Continuous Capecitabine in Advanced Breast Cancer
A Phase 2/3 study testing Capecitabine in people with Metastatic Breast Cancer, run by Hospital San Carlos, Madrid at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Capecitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 195 participants
- Where
- 1 siteSpain
- Study dates
- Sep 2005to Jan 2015
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with metastatic breast cancer
- Patients that either have received previous treatment with anthracyclines and/or taxanes or not (either as advance or in metastatic disease).
- The patient is ambulatory with a functional ECOG < 2 status (see Appendix 2).
- Patient presents, at least one lesion measurable according to RECIST criteria (see Appendix 3)
- Patients with a life expectancy of at least 3 months.
- Patients that agree to and are able to fulfill the requirements of the whole protocol through the whole study.
Who cannot join
- Patients that have previously shown unexpected severe reactions to therapy with fluoropyrimidines or with a known sensitivity to 5-fluorouracile.
- Patients previously treated with capecitabine.
- Patients with organ transplants.
- Other diseases or severe affections:
- 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.
- Patients with severe intellectual impairment, unable to carry out basic daily routines and established depression.
Show all 23Show fewer
- 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.
- Severe renal impairment (baseline creatinine clearance < 30 ml/min)
- 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.
- Patients with an active infection.
- 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.
- Patients showing the following laboratory values:
- Neutrophil count < 555 x 109/l
- Platelet count< 100 x 109/l
- Serum creatinine > 1,5 x upper normality limit
- seric bilirubin > 2,0 x upper normality limit
- ALAT, ASAT > 2,5 x upper normality limit or > 5 x upper normality limit in case of liver metastases
- 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.
- 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.
- Patients under major surgery within 4 weeks prior to study treatment or who have not completely recovered from the effects of major surgery.
- Patients who lack upper gastrointestinal tract physical integrity or with malabsorption syndrome.
- Patients who have received more than two cycles of chemotherapy for the metastatic disease.
- Patients Her2 + per FISH ó +++ Immunohistochemistry
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Trial of Continuous Versus Standard Capecitabine in Advanced Breast Cancer.
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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Capecitabine
- Keywords
- capecitabine, schedule, breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called xeloda
| Study group | Role | What they receive |
|---|---|---|
| A Cint | Active comparator | 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. Receives: Drug: Capecitabine |
| B Ccont | Experimental | 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. Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression
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).
Measured: After 1 year from the treatment start day.
Secondary outcomes (6)
Response Rate
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).
Measured: Through the study treatment, an average of 5 months.
Response Duration
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.
Measured: 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.
Time to Treatment Failure
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.
Measured: 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.
Overall Survival
An event is defined as death. A patient is censored if she does not die. The censoring date is last contact date.
Measured: Time to survival is the number of months from the study treatment start date to the date of death, assessed up to 100 months.
Clinical Benefit
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.
Measured: Months from "CR","PR" or "SD" (the first one) until Progression date, new treatment or last contact date.
Progression Free Survival
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.
Measured: Time (in months) from the moment the patient starts the study treatment to the date of progressive disease assessed up to 84 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2007 (estimated)
- Study startSep 2005
- Primary completionDec 2011
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 195 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital San Carlos, Madrid
- Sponsor type
- University, hospital or other
- Collaborators
- Complexo Hospitalario Universitario de A Coruña
- Responsible party
- Principal investigator, Miguel Martin, Hospital San Carlos, Madrid
- Investigators
- Miguel Martin, MD,PhD, Study chair, Hospital Clinico San Carlos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00418028
- Sponsor's protocol ID
- 05/237
- Other IDs
- 2004-002759-15, 2004
- Status last verified
- Feb 2019
- First submitted
- 3 Jan 2007
- Last updated
- 22 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Martin M, Martinez N, Ramos M, Calvo L, Lluch A, Zamora P, Munoz M, Carrasco E, Caballero R, Garcia-Saenz JA, Guerra E, Caronia D, Casado A, Ruiz-Borrego M, Hernando B, Chacon JI, De la Torre-Montero JC, Jimeno MA, Heras L, Alonso R, De la Haba J, Pita G, Constenla M, Gonzalez-Neira A. Standard versus continuous administration of capecitabine in metastatic breast cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a pharmacogenetic analysis. Oncologist. 2015 Feb;20(2):111-2. doi: 10.1634/theoncologist.2014-0379. Epub 2015 Jan 19.
PubMed 25601966
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial of Continuous Versus Standard Capecitabine in Advanced Breast Cancer.
- ClinicalTrials.gov ID
- NCT00418028
- Acronym / sponsor ID
- 05/237
- Conditions
- Metastatic Breast Cancer
- Keywords
- capecitabine, schedule, breast cancer
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 195 participants (actual)
- Lead sponsor
- Hospital San Carlos, MadridUniversity, hospital or other
- Collaborators
- Complexo Hospitalario Universitario de A Coruña
- Study start
- Sep 2005
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 4 Jan 2007 (estimated)
- Results
- Posted 18 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A Cint | Active comparator | Drug: CapecitabineCapecitabine 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 | Experimental | Drug: CapecitabineCapecitabine 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients diagnosed with metastatic breast cancer
- Patients that either have received previous treatment with anthracyclines and/or taxanes or not (either as advance or in metastatic disease).
- The patient is ambulatory with a functional ECOG < 2 status (see Appendix 2).
- Patient presents, at least one lesion measurable according to RECIST criteria (see Appendix 3)
- Patients with a life expectancy of at least 3 months.
Key exclusion criteria (23 listed)
- Patients that have previously shown unexpected severe reactions to therapy with fluoropyrimidines or with a known sensitivity to 5-fluorouracile.
- Patients previously treated with capecitabine.
- Patients with organ transplants.
- Other diseases or severe affections:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineAlso: xeloda | Drug | A Cint, B Ccont |
Primary outcome
Time to Progression
Time frame: 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).
6 secondary outcomes
Response Rate
Time frame: Through the study treatment, an average of 5 months.
Response Duration
Time frame: 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.
Time to Treatment Failure
Time frame: 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.
Overall Survival
Time frame: Time to survival is the number of months from the study treatment start date to the date of death, assessed up to 100 months.
Clinical Benefit
Time frame: Months from "CR","PR" or "SD" (the first one) until Progression date, new treatment or last contact date.
Progression Free Survival
Time frame: Time (in months) from the moment the patient starts the study treatment to the date of progressive disease assessed up to 84 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25601966Martin M, Martinez N, Ramos M, Calvo L, Lluch A, Zamora P, Munoz M, Carrasco E, Caballero R, Garcia-Saenz JA, Guerra E, Caronia D, Casado A, Ruiz-Borrego M, Hernando B, Chacon JI, De la Torre-Montero JC, Jimeno MA, Heras L, Alonso R, De la Haba J, Pita G, Constenla M, Gonzalez-Neira A. Standard versus continuous administration of capecitabine in metastatic breast cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a pharmacogenetic analysis. Oncologist. 2015 Feb;20(2):111-2. doi: 10.1634/theoncologist.2014-0379. Epub 2015 Jan 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miguel Martin, MD,PhD study chair
Hospital Clinico San Carlos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Capecitabine in people with Metastatic Breast Cancer, run by Hospital San Carlos, Madrid at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression (time frame: After 1 year from the treatment start day.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00418028, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2019.