Neoplasm, Malignant
Conditions
Keywords
Solid tumor, malignancy, sunitinib, pemetrexed, phase 1, neoplasms
Brief summary
This study will assess if the combination of sunitinib and pemetrexed is tolerable when coadministered at each recommended dose/schedule.
Interventions
DRUGSunitinib, Pemetrexed
Sunitinib daily by oral capsule in a continuous daily dosing regimen with pemetrexed every 3 weeks until progression or unacceptable toxicity.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of a solid malignancy that is refractory to standard therapy or for which no standard therapy exists. * Patients has a good performance status (ECOG 0 or 1)
Exclusion criteria
* Prior treatment with either pemetrexed or SU011248. * Coughing up blood within 4 weeks before starting study treatment (small amounts okey). * Hypertension that cannot be controlled by medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | End of study (up to individual discontinuation) | Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 3 or higher , dose limiting toxicities (DLT), serious adverse events, adverse events resulted in discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Up to Cycle 6 | Relative dose intensity was defined as percentage of total dose administered over total planned dose in the given period. |
| Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose | Trough concentration was defined as observed concentration at 24 hours post dose. SU012662 is an active metabolite of sunitinib. |
| AUC 0-24 of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose | AUC0-24 = Area under the plasma concentration versus time curve to 24 hours post dose was calculated using the linear/logarithmic trapezoidal method. SU012662 is an active metabolite of sunitinib. |
| Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose | Tmax = Time to maximum plasma concentration. SU012662 is an active metabolite of sunitinib. |
| Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm | Up to Cycle 5 (end of study) | Relative dose intensity was defined as percentage of total dose administered over total planned dose in the given period. |
| AUC0-∞ of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | AUC0-∞ = Area under the plasma concentration versus time curve from zero time to infinity was calculated as the sum of AUClast and (Ct\*/kel), where Ct\* was the estimated concentration at the time of the last quantifiable concentration, kel was terminal phase rate constant that is estimated as the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm (ln) transformed concentration-time profile. |
| Terminal Phase Elimination Half-Life (T1/2) of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | Terminal phase elimination half-life was calculated as natural logarithm of 2 (ln2) divided by the rate constant for terminal phase (kel). |
| Trough Concentrations of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) After Coadministration of Sunitinib 50 mg/Day and Pemetrexed 500 mg/m^2 (Cycle 1 Day 1), Followed by Sunitinib 50 mg/Day on Schedule-2/1 at Cycle 1 Day 14 or 15 | Cycle 1 Day 14 (or 15): approximately 24 hours after the previous dose | Trough concentration was defined as observed concentration at 24 hours post dose. SU012662 is an active metabolite of sunitinib. |
| Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | End of study (Up to individual study discontinuation) | Complete response (CR): disappearance of all target lesions; Partial response (PR): \>=30% decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD; Progressive disease (PD): \>=20% increase in the SLD of the target lesions taking as a reference the smallest SLD recorded since the treatment started, or the appearance of \>=1 new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as a reference the smallest SLD since the treatment started. |
| Maximum Concentration of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing Sunitinib 37.5 mg was administered continuously on a daily basis. Pemetrexed 500 mg/m\^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle. | 6 |
| Sunitinib 50 mg/Day Schedule-2/1 Sunitinib 50.0 mg was administered continuously on a daily basis for 2 weeks, followed by 1 week off treatment.
Pemetrexed 500 mg/m\^2 was administered as intravenous infusion over 10 minutes on the first day (Day 1) of each 21-day cycle. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Global Deterioration of Health Status | 1 | 0 |
| Overall Study | Objective Progression or Relapse | 3 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib 50 mg/Day Schedule-2/1 | Total |
|---|---|---|---|
| Age, Customized 20-44 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 45- 64 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Customized >=65 years | 2 Participants | 4 Participants | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score 0 | 2 Participants | 4 Participants | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Score 1 | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 1 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 3 or higher , dose limiting toxicities (DLT), serious adverse events, adverse events resulted in discontinuation.
Time frame: End of study (up to individual discontinuation)
Population: All subjects who received at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Number of Participants With Adverse Events | Any adverse events | 6 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Number of Participants With Adverse Events | Any dose limiting toxicities | 0 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Number of Participants With Adverse Events | Any serious adverse events | 2 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Number of Participants With Adverse Events | Any Grade-3 or -4 adverse events | 6 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Number of Participants With Adverse Events | Any Grade-5 adverse events (= death) | 0 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Number of Participants With Adverse Events | Discontinuation due to adverse events | 1 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Number of Participants With Adverse Events | Any Grade-5 adverse events (= death) | 0 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Number of Participants With Adverse Events | Any adverse events | 6 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Number of Participants With Adverse Events | Any Grade-3 or -4 adverse events | 3 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Number of Participants With Adverse Events | Any dose limiting toxicities | 0 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Number of Participants With Adverse Events | Discontinuation due to adverse events | 1 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Number of Participants With Adverse Events | Any serious adverse events | 1 Participants |
Secondary
AUC 0-24 of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1
AUC0-24 = Area under the plasma concentration versus time curve to 24 hours post dose was calculated using the linear/logarithmic trapezoidal method. SU012662 is an active metabolite of sunitinib.
Time frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose
Population: Participants who provided a plasma concentration data was included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | AUC 0-24 of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Sunitinib | 1190 nanogram*hour/mL | Standard Deviation 247 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | AUC 0-24 of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | SU012662 | 675 nanogram*hour/mL | Standard Deviation 107 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | AUC 0-24 of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Total Drug | 1866 nanogram*hour/mL | Standard Deviation 269 |
Secondary
AUC0-∞ of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1
AUC0-∞ = Area under the plasma concentration versus time curve from zero time to infinity was calculated as the sum of AUClast and (Ct\*/kel), where Ct\* was the estimated concentration at the time of the last quantifiable concentration, kel was terminal phase rate constant that is estimated as the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm (ln) transformed concentration-time profile.
Time frame: Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Population: Participants who provided a plasma concentration data was included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | AUC0-∞ of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | 191 microgram*hour/mL | Standard Deviation 36.3 |
Secondary
Maximum Concentration of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1
Time frame: Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Population: Participants who provided a plasma concentration data was included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Maximum Concentration of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | 163 microgram/mL | Standard Deviation 30.7 |
Secondary
Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants
Complete response (CR): disappearance of all target lesions; Partial response (PR): \>=30% decrease in the sum of the longest dimensions (SLD) of the target lesions taking as a reference the baseline SLD; Progressive disease (PD): \>=20% increase in the SLD of the target lesions taking as a reference the smallest SLD recorded since the treatment started, or the appearance of \>=1 new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as a reference the smallest SLD since the treatment started.
Time frame: End of study (Up to individual study discontinuation)
Population: Evaluable subjects = defined as all subjects who met all the following 3 requirements: 1) met the eligibility (inclusion and exclusion) criteria, 2) received at least 1 dose of the study drug, and 3) assessed appropriately at the baseline and had a measurable lesion based on the RECIST.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Complete Response (CR) | 0 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Partial Response (PR) | 1 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Stable Disease (SD) | 2 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Progressive Disease (PD) | 1 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Not Evaluable (NE) | 0 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Objective Response (CR+PR) | 1 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Stable Disease (SD) >=184 days | 0 Participants |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Clinical Benefit (CR+PR+SD >=184 days) | 1 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Clinical Benefit (CR+PR+SD >=184 days) | 1 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Complete Response (CR) | 0 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Not Evaluable (NE) | 0 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Partial Response (PR) | 0 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Stable Disease (SD) >=184 days | 1 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Stable Disease (SD) | 3 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Objective Response (CR+PR) | 0 Participants |
| Sunitinib 50 mg/Day Schedule-2/1 | Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of Participants | Progressive Disease (PD) | 1 Participants |
Secondary
Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm
Relative dose intensity was defined as percentage of total dose administered over total planned dose in the given period.
Time frame: Up to Cycle 5 (end of study)
Population: Full analysis set = defined as all enrolled patients. n = number of participants assessed for the relative dose intensity in the given period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm | Cycle 1 (n=6) | 92.0 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm | Cycle 2 (n=6) | 54.8 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm | Cycle 3 (n=4) | 46.0 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm | Cycle 4 (n=4) | 55.6 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 37.5 mg/Day Continuous Daily Dosing Treatment Arm | Cycle 5 (n=1) | 44.4 percent of total planned dose |
Secondary
Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm
Relative dose intensity was defined as percentage of total dose administered over total planned dose in the given period.
Time frame: Up to Cycle 6
Population: Full analysis set = defined as all enrolled patients. n = number of participants assessed for the relative dose intensity in the given period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Cycle 1 (n=6) | 87.5 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Cycle 2 (n=5) | 80.4 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Cycle 3 (n=4) | 53.6 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Cycle 4 (n=3) | 50.0 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Cycle 5 (n=3) | 50.0 percent of total planned dose |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Sunitinib Relative Dose Intensity in the Sunitinib 50 mg/Day Schedule-2/1 Treatment Arm | Cycle 6 (n=3) | 50.0 percent of total planned dose |
Secondary
Terminal Phase Elimination Half-Life (T1/2) of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1
Terminal phase elimination half-life was calculated as natural logarithm of 2 (ln2) divided by the rate constant for terminal phase (kel).
Time frame: Cycle 2 Day 1: Pre-dose, 10 minutes after the start of infusion (immediately before the end of infusion), and 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Population: Participants who provided a plasma concentration data was included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Terminal Phase Elimination Half-Life (T1/2) of Pemetrexed Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | 2.754 hours | Standard Deviation 0.531 |
Secondary
Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1
Tmax = Time to maximum plasma concentration. SU012662 is an active metabolite of sunitinib.
Time frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose
Population: Participants who provided a plasma concentration data was included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Sunitinib | 4 hours |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | SU012662 | 4 hours |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Total Drug | 4 hours |
Secondary
Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1
Trough concentration was defined as observed concentration at 24 hours post dose. SU012662 is an active metabolite of sunitinib.
Time frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose
Population: Participants who provided a plasma concentration data was included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Sunitinib: Trough concentration | 45.6 nanogram/mL | Standard Deviation 11.7 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Sunitinib: Maximum concentration | 59.9 nanogram/mL | Standard Deviation 10.9 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | SU012662: Trough concentration | 25.1 nanogram/mL | Standard Deviation 5.08 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | SU012662: Maximum concentration | 31.6 nanogram/mL | Standard Deviation 5.49 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Total drug: Trough concentration | 70.6 nanogram/mL | Standard Deviation 13.9 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough and Maximum Concentration of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) Following Continuous Daily Dosing of Sunitinib 37.5 mg/Day in Combination With Pemetrexed 500 mg/m^2 at Cycle 2 Day 1 | Total drug: Maximum concentration | 91.5 nanogram/mL | Standard Deviation 14.2 |
Secondary
Trough Concentrations of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) After Coadministration of Sunitinib 50 mg/Day and Pemetrexed 500 mg/m^2 (Cycle 1 Day 1), Followed by Sunitinib 50 mg/Day on Schedule-2/1 at Cycle 1 Day 14 or 15
Trough concentration was defined as observed concentration at 24 hours post dose. SU012662 is an active metabolite of sunitinib.
Time frame: Cycle 1 Day 14 (or 15): approximately 24 hours after the previous dose
Population: Participants who provided a plasma concentration data was included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough Concentrations of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) After Coadministration of Sunitinib 50 mg/Day and Pemetrexed 500 mg/m^2 (Cycle 1 Day 1), Followed by Sunitinib 50 mg/Day on Schedule-2/1 at Cycle 1 Day 14 or 15 | Sunitinib | 78.5 nanogram/mL | Standard Deviation 22.2 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough Concentrations of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) After Coadministration of Sunitinib 50 mg/Day and Pemetrexed 500 mg/m^2 (Cycle 1 Day 1), Followed by Sunitinib 50 mg/Day on Schedule-2/1 at Cycle 1 Day 14 or 15 | SU012662 | 38.2 nanogram/mL | Standard Deviation 17 |
| Sunitinib 37.5 mg/Day Continuous Daily Dosing | Trough Concentrations of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) After Coadministration of Sunitinib 50 mg/Day and Pemetrexed 500 mg/m^2 (Cycle 1 Day 1), Followed by Sunitinib 50 mg/Day on Schedule-2/1 at Cycle 1 Day 14 or 15 | Total Drug | 117 nanogram/mL | Standard Deviation 30.8 |