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
  Purpose

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


Condition Intervention Phase
Neoplasm, Malignant
Drug: Sunitinib, Pemetrexed
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study Of Sunitinib (SU011248) In Combination With Pemetrexed In Patients With Advanced Solid Malignancies In Japan

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 12
Study Start Date: August 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Sutent, SU011248, Alimta
Experimental: 2/1 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

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732992

Locations
Japan
Pfizer Investigational Site
Osakasayama-shi, Osaka, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00732992     History of Changes
Other Study ID Numbers: A6181165
Study First Received: August 8, 2008
Results First Received: October 27, 2010
Last Updated: March 15, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Pfizer:
Solid tumor
malignancy
sunitinib
pemetrexed
phase 1
neoplasms

Additional relevant MeSH terms:
Neoplasms
Pemetrexed
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014