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

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

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

Study Overview

• Status: Completed
• Conditions: Neoplasm, Malignant
• Intervention / Treatment: Drug: Sunitinib, Pemetrexed; Drug: Sunitinib, Pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Osakasayama-shi, Osaka, Japan
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Okamoto I, Shimizu T, Miyazaki M, Tsurutani J, Ichikawa Y, Terashima M, Takeda M, Fumita S, Ohki E, Kimura N, Hashimoto J, Nakagawa K. Feasibility study of two schedules of sunitinib in combination with pemetrexed in patients with advanced solid tumors. Invest New Drugs. 2012 Apr;30(2):639-46. doi: 10.1007/s10637-010-9565-5. Epub 2010 Oct 20.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: August 8, 2008
• First Submitted That Met QC Criteria: August 11, 2008
• First Posted (Estimate): August 12, 2008

Study Record Updates

• Last Update Posted (Estimate): March 17, 2011
• Last Update Submitted That Met QC Criteria: March 15, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: sunitinib; phase 1; Solid tumor; neoplasms; malignancy; pemetrexed
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Folic Acid Antagonists; Sunitinib; Pemetrexed
• Other Study ID Numbers: A6181165