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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00732992
First received: August 8, 2008
Last updated: March 15, 2011
Last verified: March 2011

August 8, 2008
March 15, 2011
August 2008
November 2009   (final data collection date for primary outcome measure)
Number of Participants With Adverse Events [ Time Frame: End of study (up to individual discontinuation) ] [ Designated as safety issue: Yes ]
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.
The overall safety including occurrence of Dose Limiting Toxicity of the combination of pemetrexed with sunitinib [ Time Frame: End of study ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00732992 on ClinicalTrials.gov Archive Site
  • Sunitinib Relative Dose Intensity in the "Sunitinib 37.5 mg/Day Continuous Daily Dosing" Treatment Arm [ Time Frame: Up to Cycle 5 (end of study) ] [ Designated as safety issue: No ]
    Relative dose intensity was defined as percentage of total dose administered over total planned dose in the given period.
  • Sunitinib Relative Dose Intensity in the "Sunitinib 50 mg/Day Schedule-2/1" Treatment Arm [ Time Frame: Up to Cycle 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 2 Day 1: Pre-dose and 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
  • 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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1 Day 14 (or 15): approximately 24 hours after the previous dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of study (Up to individual study discontinuation) ] [ Designated as safety issue: No ]
    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.
  • Pharmacokinetic parameters of pemetrexed, SU011248, and SU012662 [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Type, incidence, severity, timing , seriousness, and relatedness of adverse events, laboratory abnormalities [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Dose reductions and cycle delays [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Antitumor activity of sunitinib in combination with pemetrexed [ Time Frame: End of study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasm, Malignant
  • 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 Name: 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 Name: Sutent, SU011248, Alimta
  • Experimental: CDD
    Intervention: Drug: Sunitinib, Pemetrexed
  • Experimental: 2/1
    Intervention: Drug: Sunitinib, Pemetrexed
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. Epub 2010 Oct 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
November 2009
November 2009   (final data collection date for primary outcome measure)

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.
Both
20 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00732992
A6181165
No
Director, Clinical Trial Disclosure Group, Pfizer, Inc.
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP