Study Of Sunitinib With Capecitabine In Breast Cancer

Study Overview
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Brief Summary
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To evaluate efficacy, safety and pharmacokinetics of sunitinib plus Capecitabine in Japanese patients with advanced/metastatic breast cancer.

Official Title
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A Phase II Study Of Sunitinib Malate In Combination With Capecitabine In Patients With Advanced Or Metastatic Breast Cancer

Conditions
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Advanced/Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically-proven diagnosis of breast adenocarcinoma that is not amenable to surgery, radiation, or combined modality therapy with curative intent Measurable disease as per RECIST. Measurable lesions that have been previously irradiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy. Prior treatment with an anthracycline and a taxane in the neoadjuvant, adjuvant or metastatic disease settings. Exclusion Criteria: Histology of inflammatory carcinoma with no other measurable disease. Patients with histology of inflammatory carcinoma are allowed on study if they have measurable disease. Brain metastases, spinal cord compression, or carcinomatous meningitis, or leptomeningeal disease. Prior treatment with 5-fluorouracil (5-FU) and 5-FU derivatives such as Furtulon (5'-DFUR), Futraful/ Sunfural (tegafur), UFT/UFT-E (tegafur/uracil), TS-1 (tegafur/gimeracil/oteracil) or Mifurol (carmofur) in metastatic disease setting

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Capecitabine<br>* Capecitabine 1000 mg/m2, twice daily, for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles<br>Drug: Sunitinib<br>* Sunitinib 37.5 mg daily, continuous dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Response Based on Data Review Committee's Assessment | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST). CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the longest dimensions (LDs) of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Response Based on Investigator's Assessment | Number of participants with objective response based on assessment of confirmed CR or confirmed PR according to RECIST. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study. | 
| Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment | Number of participants with confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as a reference the baseline sum LD according to RECIST. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of LDs since treatment started. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. | 
| Number of Subjects With CBR Based on Investigator's Assessment | Number of participants with confirmed CR, PR or SD for at least 24 weeks on study according to RECIST. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as a reference the baseline sum LD according to RECIST. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of LDs since treatment started. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study. | 
| Progression-Free Survival (PFS) | Based on Data Review Committee's Assessment. PFS is defined as the time from the start of study treatment to first documentation of objective tumor progression, or to death on study due to any cause, whichever occurred first. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. | 
| Time to Tumor Progression (TTP) | Based on Data Review Committee's Assessment. TTP is defined as the time from the start of study treatment to first documentation of objective tumor progression. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. | 
| Duration of Objective Tumor Response (DR) | Based on Data Review Committee's Assessment. DR is defined as the time from the first documentation of objective tumor response (confirmed CR or PR) to the first documentation of disease progression or to death due to cancer, whichever occurred first. CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. | 
| Time to Objective Tumor Response (TTR) | Based on Data Review Committee's Assessment. TTR is defined as the time from the start of study treatment to first documentation of objective tumor response (confirmed CR or PR). CR is defined as disappearance of all target and non-target lesions. PR is defined as ≥30% decrease in sum of the LDs of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation ≥4 weeks after initial documentation of response. | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. Up to 28 days after the last administration of the study drug. | 
| Overall Survival (OS) | OS is defined as the time from the start of study treatment to death due to any cause. OS data is censored on the last day they were known to be alive in the absence of confirmation of death. | A survival survey was conducted at least every 6 months after the completion of study treatment or withdrawal from the study. | 
| Trough Plasma Concentration (Ctrough) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 is a metabolite of sunitinib. Trough plasma concentration (Ctrough) means the concentration prior to study drug administration. The Ctrough for total drug (sunitinib+SU012662) was calculated as the mean of the Ctrough of total drug from individual participant. | Days 14 and 15 of Cycle 1 | 
| Tmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 is a metabolite of sunitinib. Tmax means a time to first occurrence of maximum observed plasma concentration (Cmax). The Tmax for total drug (sunitinib+SU012662) was calculated as the median of the Tmax of total drug from individual participant. | Days 14 and 15 of Cycle 1 | 
| Cmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 is a metabolite of sunitinib. Cmax means a maximum observed plasma concentration. The Cmax for total drug (sunitinib+SU012662) was calculated as the mean of the Cmax of total drug from individual participant. | Days 14 and 15 of Cycle 1 | 
| AUC(0-24) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 is a metabolite of sunitinib. AUC(0-24) means an area under the plasma concentration time curve from time zero to 24 hours post-dose. The AUC(0-24) for total drug (sunitinib+SU012662) was calculated as the mean of the AUC(0-24) of total drug from individual participant. | Days 14 and 15 of Cycle 1 | 
| Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Tmax means a time to first occurrence of maximum observed plasma concentration (Cmax). 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil | Day 14 of Cycle 1 | 
| Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Cmax means a maximum observed plasma concentration. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil | Day 14 of Cycle 1 | 
| AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | AUC(0-inf) means an area under the plasma concentration time curve from time zero to Infinity. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil | Day 14 of Cycle 1 | 
| t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | t1/2 means a terminal phase half-life. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil | Day 14 of Cycle 1 |