Advanced/Metastatic Breast Cancer
Conditions
Brief summary
To evaluate efficacy, safety and pharmacokinetics of sunitinib plus Capecitabine in Japanese patients with advanced/metastatic breast cancer.
Interventions
DRUGCapecitabine
Capecitabine 1000 mg/m2, twice daily, for 2 consecutive weeks, followed by a 1-week rest period and given as 3-week cycles
DRUGSunitinib
Sunitinib 37.5 mg daily, continuous dosing
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Based on Data Review Committee's Assessment | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8. | 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. |
| Number of Subjects With CBR Based on Investigator's Assessment | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study. | 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. |
| Progression-Free Survival (PFS) | 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. | 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. |
| Time to Tumor Progression (TTP) | 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. | 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. |
| Duration of Objective Tumor Response (DR) | 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. | 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. |
| Time to Objective Tumor Response (TTR) | 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. | 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. |
| Overall Survival (OS) | A survival survey was conducted at least every 6 months after the completion of study treatment or withdrawal from the study. | 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. |
| Number of Participants With Objective Response Based on Investigator's Assessment | Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study. | 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. |
| Tmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Days 14 and 15 of Cycle 1 | 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. |
| Cmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Days 14 and 15 of Cycle 1 | 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. |
| AUC(0-24) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Days 14 and 15 of Cycle 1 | 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. |
| Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Day 14 of Cycle 1 | 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 |
| Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Day 14 of Cycle 1 | Cmax means a maximum observed plasma concentration. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil |
| AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Day 14 of Cycle 1 | 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 |
| t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Day 14 of Cycle 1 | t1/2 means a terminal phase half-life. 5'-DFCR = 5'-deoxy-5-fluorocytidine, 5'-DFUR = 5'-deoxy-5-fluorouridine, 5-FU = 5-fluorouracil |
| Trough Plasma Concentration (Ctrough) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Days 14 and 15 of Cycle 1 | 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. |
Countries
Japan
Participant flow
Pre-assignment details
The study consisted of 2 cohorts. Cohort 1 enrolled 6 participants. All adverse events in Cohort 1 were evaluated at the end of Cycle 2, and study continuation to Cohort 2 was determined based on the recommendation from the Independent Safety Monitoring Committee. Cohort 2 consisted of 63 participants, including the 6 participants in Cohort 1.
Participants by arm
| Arm | Count |
|---|---|
| SUNITINIB+CAPECITABINE Sunitinib was administered orally from Day 1 at the starting dose of 37.5 mg/day on a continuous daily dosing schedule in 21-day cycles. Capecitabine was administered orally from Days 1 to 14 every 21 days at a starting dose of 2,000 mg/m\^2/day. Participants were monitored for toxicity, and sunitinib and/or capecitabine dosing could be interrupted or reduced according to individual tolerance. Participants with progressive disease (PD) or intolerable toxicity were considered for discontinuation from the study. | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Domestic circumstances | 1 |
| Overall Study | Objective progression or relapse | 51 |
| Overall Study | Results of other clinical study | 2 |
| Overall Study | Target lesion cannot be evaluated | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | SUNITINIB+CAPECITABINE |
|---|---|
| Age Continuous | 52.9 years |
| Age, Customized >=20 years and 44 years >= | 13 participants |
| Age, Customized >=45 years and 64 years >= | 43 participants |
| Age, Customized >=65 years | 7 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score 0 | 57 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score 1 | 6 participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 63 / 63 |
| serious Total, serious adverse events | 17 / 63 |
Outcome results
Primary
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.
Time frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8.
Population: Full Analysis Set (FAS) is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUNITINIB+CAPECITABINE | Number of Participants With Objective Response Based on Data Review Committee's Assessment | Total Number of Participants with CR+PR | 19 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Objective Response Based on Data Review Committee's Assessment | Complete Response (CR) | 0 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Objective Response Based on Data Review Committee's Assessment | Partial Response (PR) | 19 participants |
95% CI: [19.2, 43]
Secondary
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.
Time frame: Days 14 and 15 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants (Cohort 1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SUNITINIB+CAPECITABINE | AUC(0-24) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Total drug (Sunitinib+SU012662) | 2590 nanogram∙hour/milliliter | Standard Deviation 658 |
| SUNITINIB+CAPECITABINE | AUC(0-24) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Sunitinib | 1886 nanogram∙hour/milliliter | Standard Deviation 524 |
| SUNITINIB+CAPECITABINE | AUC(0-24) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 | 704 nanogram∙hour/milliliter | Standard Deviation 176 |
Secondary
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
Time frame: Day 14 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants(Cohort 1).~n=Number of participants with analyzable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SUNITINIB+CAPECITABINE | AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Capecitabine (n=3) | 5505 nanogram∙hour/milliliter | Standard Deviation 151 |
| SUNITINIB+CAPECITABINE | AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFCR (n=4) | 13177 nanogram∙hour/milliliter | Standard Deviation 7038 |
| SUNITINIB+CAPECITABINE | AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFUR (n=3) | 12236 nanogram∙hour/milliliter | Standard Deviation 3777 |
| SUNITINIB+CAPECITABINE | AUC(0-inf) for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5-FU (n=3) | 635 nanogram∙hour/milliliter | Standard Deviation 152 |
Secondary
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
Time frame: Day 14 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 subjects (Cohort 1). n=Number of subjects with analyzable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SUNITINIB+CAPECITABINE | Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFCR (n=4) | 5758 nanogram/milliliter | Standard Deviation 2405 |
| SUNITINIB+CAPECITABINE | Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFUR (n=4) | 6885 nanogram/milliliter | Standard Deviation 4130 |
| SUNITINIB+CAPECITABINE | Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5-FU (n=4) | 387 nanogram/milliliter | Standard Deviation 249 |
| SUNITINIB+CAPECITABINE | Cmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Capecitabine (n=4) | 3773 nanogram/milliliter | Standard Deviation 1907 |
Secondary
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.
Time frame: Days 14 and 15 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants (Cohort 1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SUNITINIB+CAPECITABINE | Cmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Sunitinib | 87.7 nanogram/milliliter | Standard Deviation 27.6 |
| SUNITINIB+CAPECITABINE | Cmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 | 33.9 nanogram/milliliter | Standard Deviation 8.43 |
| SUNITINIB+CAPECITABINE | Cmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Total Drug (Sunitinib+SU012662) | 119 nanogram/milliliter | Standard Deviation 31.7 |
Secondary
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.
Time frame: 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.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.~Nineteen participants with objective tumor response were analyzed for DR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SUNITINIB+CAPECITABINE | Duration of Objective Tumor Response (DR) | 4.1 months |
Secondary
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.
Time frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUNITINIB+CAPECITABINE | Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment | Total Number of Participants with CBR | 32 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment | Complete Response (CR) | 0 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment | Partial Response (PR) | 19 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Clinical Benefit Response (CBR) Based on Data Review Committee's Assessment | Stable Disease (SD) >= 168 days | 13 participants |
95% CI: [37.9, 63.6]
Secondary
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.
Time frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUNITINIB+CAPECITABINE | Number of Participants With Objective Response Based on Investigator's Assessment | Total Number of Participants with CR+PR | 17 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Objective Response Based on Investigator's Assessment | Complete Response (CR) | 0 participants |
| SUNITINIB+CAPECITABINE | Number of Participants With Objective Response Based on Investigator's Assessment | Partial Response (PR) | 17 participants |
95% CI: [16.6, 39.7]
Secondary
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.
Time frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of study.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SUNITINIB+CAPECITABINE | Number of Subjects With CBR Based on Investigator's Assessment | Total Number of Participatnts with CBR | 33 participants |
| SUNITINIB+CAPECITABINE | Number of Subjects With CBR Based on Investigator's Assessment | Complete Response (CR) | 0 participants |
| SUNITINIB+CAPECITABINE | Number of Subjects With CBR Based on Investigator's Assessment | Partial Response (PR) | 17 participants |
| SUNITINIB+CAPECITABINE | Number of Subjects With CBR Based on Investigator's Assessment | Stable Disease (SD) >= 168 days | 16 participants |
95% CI: [39.4, 65.1]
Secondary
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.
Time frame: A survival survey was conducted at least every 6 months after the completion of study treatment or withdrawal from the study.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SUNITINIB+CAPECITABINE | Overall Survival (OS) | 20.0 months |
Secondary
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.
Time frame: 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.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SUNITINIB+CAPECITABINE | Progression-Free Survival (PFS) | 5.3 months |
Secondary
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
Time frame: Day 14 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants (Cohort 1).~n=Number of participants with analyzable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SUNITINIB+CAPECITABINE | t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Capecitabine (n=3) | 0.80 hours | Standard Deviation 0.34 |
| SUNITINIB+CAPECITABINE | t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFUR (n=3) | 0.73 hours | Standard Deviation 0.05 |
| SUNITINIB+CAPECITABINE | t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5-FU (n=3) | 0.77 hours | Standard Deviation 0.06 |
| SUNITINIB+CAPECITABINE | t1/2 for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFCR (n=4) | 1.01 hours | Standard Deviation 0.19 |
Secondary
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.
Time frame: 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.
Population: FAS is defined as the population of all participants who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.~Twenty three participants with objective tumor response were analyzed for TTR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SUNITINIB+CAPECITABINE | Time to Objective Tumor Response (TTR) | 1.4 months |
Secondary
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.
Time frame: 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.
Population: FAS is defined as the population of all enrolled patients who are diagnosed as having advanced/metastatic breast cancer and received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SUNITINIB+CAPECITABINE | Time to Tumor Progression (TTP) | 5.3 months |
Secondary
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
Time frame: Day 14 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants (Cohort 1).~n=Number of participants with analyzable data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SUNITINIB+CAPECITABINE | Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | Capecitabine (n=4) | 0.75 hours |
| SUNITINIB+CAPECITABINE | Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFCR (n=4) | 1 hours |
| SUNITINIB+CAPECITABINE | Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5'-DFUR (n=4) | 1.5 hours |
| SUNITINIB+CAPECITABINE | Tmax for Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR and 5-FU) | 5-FU (n=4) | 1.5 hours |
Secondary
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.
Time frame: Days 14 and 15 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants (Cohort 1).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SUNITINIB+CAPECITABINE | Tmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Sunitinib | 10 hours |
| SUNITINIB+CAPECITABINE | Tmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 | 3 hours |
| SUNITINIB+CAPECITABINE | Tmax for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Total Drug (Sunitinib+SU012662) | 6 hours |
Secondary
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.
Time frame: Days 14 and 15 of Cycle 1
Population: Pharmacokinetic parameters are estimated for the initial 6 participants (Cohort 1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SUNITINIB+CAPECITABINE | Trough Plasma Concentration (Ctrough) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Sunitinib | 68.7 nanogram/milliliter | Standard Deviation 16.7 |
| SUNITINIB+CAPECITABINE | Trough Plasma Concentration (Ctrough) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | SU012662 | 30.8 nanogram/milliliter | Standard Deviation 10.2 |
| SUNITINIB+CAPECITABINE | Trough Plasma Concentration (Ctrough) for Sunitinib, SU012662, and Total Drug (Sunitinib+SU012662) | Total Drug (Sunitinib+SU012662) | 99.5 nanogram/milliliter | Standard Deviation 24.1 |