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A Safety Study Of Sunitinib In Combination With Pemetrexed In Patients With Advanced Solid Malignancies

Phase 1
Completed
Conditions
Neoplasm, Malignant
Interventions
Registration Number
NCT00732992
Lead Sponsor
Pfizer
Brief Summary

This study will assess if the combination of sunitinib and pemetrexed is tolerable when coadministered at each recommended dose/schedule.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
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)
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CDDSunitinib, Pemetrexed-
2/1Sunitinib, Pemetrexed-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse EventsEnd 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 Outcome Measures
NameTimeMethod
Sunitinib Relative Dose Intensity in the "Sunitinib 37.5 mg/Day Continuous Daily Dosing" Treatment ArmUp 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.

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 1Cycle 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 1Cycle 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.

Sunitinib Relative Dose Intensity in the "Sunitinib 50 mg/Day Schedule-2/1" Treatment ArmUp to Cycle 6

Relative dose intensity was defined as percentage of total dose administered over total planned dose in the given period.

Summary of Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST): Number of ParticipantsEnd 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.

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 1Cycle 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.

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 1Cycle 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 1Cycle 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 1Cycle 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 15Cycle 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.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇯🇵

Osakasayama-shi, Osaka, Japan

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