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

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

Official Title
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Phase 1 Study Of Sunitinib (SU011248) In Combination With Pemetrexed In Patients With Advanced Solid Malignancies In Japan

Conditions
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Neoplasm, Malignant

Intervention / Treatment
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* Drug: Sunitinib, Pemetrexed
* Drug: Sunitinib, Pemetrexed


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDD<br> | Drug: Sunitinib, Pemetrexed<br>* Sunitinib daily by oral capsule in a continuous daily dosing regimen with pemetrexed every 3 weeks until progression or unacceptable toxicity.<br>* Other names: Sutent, SU011248, Alimta;|
| Experimental: 2/1<br> | Drug: Sunitinib, Pemetrexed<br>* Sunitinib daily by oral capsule administered for 2 weeks out of every 3 weeks with pemetrexed every 3 weeks until progression or unacceptable toxicity.<br>* Other names: Sutent, SU011248, Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | End of study (up to individual discontinuation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose | 
| 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. | 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 |  | 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. | 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). | 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. | 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. | End of study (Up to individual study discontinuation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumor, malignancy, sunitinib, pemetrexed, phase 1, neoplasms