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| ID | Type | Description | Link |
|---|---|---|---|
| 2004-002759-15 | EudraCT Number |
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| Name | Class |
|---|---|
| Complexo Hospitalario Universitario de A Coruña | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capecitabine | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | After 1 year from the treatment start day. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Through the study treatment, an average of 5 months. |
| Response Duration |
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Inclusion Criteria
Exclusion criteria:
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.
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Miguel Martin, MD,PhD | Hospital Clinico San Carlos | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Clinico San Carlos | Madrid | 28040 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25601966 | Derived | 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. |
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Between November 2004 and August 2010, 195 patients were randomly assigned to Cint (97) and Ccont (98) in 13 GEICAM sites in Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (Cint) | 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. 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. |
| FG001 | Arm B (Ccont) | 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: 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A (Cint) | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | A total of 192 patients (95 in Arm A and 97 in Arm B) were considered for this analysis but 36 were censored (23 in Arm A and 13 in Arm B). Patients censored are those that did not progress or die due to progressive disease during the study treatment. | Posted | Median | 95% Confidence Interval | months | After 1 year from the treatment start day. |
|
During the study treatment (Metastatic Breast Cancer patients), up to 30 weeks approximately.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | A Cint | 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: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash: hand-foot skin reaction | Skin and subcutaneous tissue disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| The Oncologist 2015;20:1-2 http://www.theoncologist.com/ Scientific Director and CEO | GEICAM (Grupo Español de Investigación en Cancer de Mama) | +34916592870 | geicam@geicam.org |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
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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 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. | 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. | 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. | 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. | Time (in months) from the moment the patient starts the study treatment to the date of progressive disease assessed up to 84 months. |
| BG001 | Arm B (Ccont) | 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: 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Arm B (Ccont) | 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. |
|
|
|
| Secondary | 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). | There were 95 patients in Arm A and 97 patients in Arm B. There were 13 patients without response evaluation (9 in Arm A and 4 in Arm B). | Posted | Count of Participants | Participants | Through the study treatment, an average of 5 months. |
|
|
|
|
| Secondary | 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. | From 192 patients (95 in Arm A and 97 in Arm B), 61 patients had Complete Response or Partial Response (30 in Arm A and 31 in Arm B). | Posted | Median | 95% Confidence Interval | Months | 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. |
|
|
|
|
| Secondary | 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. | This outcome only was analyzed in the Per Protocol Population (182 patients). | Posted | Median | 95% Confidence Interval | Months | 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. |
|
|
|
|
| Secondary | Overall Survival | An event is defined as death. A patient is censored if she does not die. The censoring date is last contact date. | Posted | Median | 95% Confidence Interval | Months | Time to survival is the number of months from the study treatment start date to the date of death, assessed up to 100 months. |
|
|
|
|
| Secondary | 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. | Only 179 patients had tumor evaluation data. | Posted | Count of Participants | Participants | Months from "CR","PR" or "SD" (the first one) until Progression date, new treatment or last contact date. |
|
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | Months | Time (in months) from the moment the patient starts the study treatment to the date of progressive disease assessed up to 84 months. |
|
|
|
|
| 13 |
| 95 |
| 81 |
| 95 |
| EG001 | B Ccont | 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. 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. | 4 | 97 | 51 | 97 |
| Febrile neutropenia | Infections and infestations |
|
| Obstruction | Gastrointestinal disorders |
|
| Ventricular arrhythmia | Cardiac disorders |
|
| Mucositis/stomatitis | Gastrointestinal disorders |
|
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders |
|
| Infection with unknown ANC | Infections and infestations |
|
| Rash: hand-foot skin reaction | Skin and subcutaneous tissue disorders |
|
| Renal failure | Renal and urinary disorders |
|
| Dizziness | Nervous system disorders |
|
| Grade 3-4 Thrombocytopenia | Blood and lymphatic system disorders |
|
| Grade 3-4 Neutropenia | Blood and lymphatic system disorders |
|
| Grade 3-4 Diarrhea | Gastrointestinal disorders |
|
| Mucositis/stomatitis (functional/symptomatic) | Gastrointestinal disorders |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |