This study will assess if the combination of sunitinib and pemetrexed is tolerable when coadministered at each recommended dose/schedule.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Sunitinib daily by oral capsule in a continuous daily dosing regimen with pemetrexed every 3 weeks until progression or unacceptable toxicity.
Sunitinib daily by oral capsule administered for 2 weeks out of every 3 weeks with pemetrexed every 3 weeks until progression or unacceptable toxicity.
Pfizer Investigational Site
Osakasayama-shi, Osaka, Japan
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)
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)
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
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
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
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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
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
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
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
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
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)