Vatalanib and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors
RATIONALE: Vatalanib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vatalanib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib when given together with pemetrexed disodium in treating patients with advanced solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: pemetrexed disodium
Other: pharmacological study
Procedure: ultrasound imaging
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of PTK/ZK in Combination With Pemetrexed Disodium (ALIMTA)|
- Overall toxicity incidence as well as toxicity profiles as measured by dose level, patient, and primary disease site as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Dose-limiting toxicity and maximum tolerated dose (MTD) of vatalanib when administered with pemetrexed disodium as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Pharmacokinetics of treatment, including AUC, C-max, half-life, and clearance obtained in patients treated at the MTD [ Time Frame: At different time points on day 1 of each course ] [ Designated as safety issue: No ]
- Expression of functionally relevant polymorphisms in genes that encode proteins involved in the transport and activation of pemetrexed disodium in patients treated at the MTD [ Designated as safety issue: No ]
- Correlation of expression of these polymorphisms with clinical outcomes (toxicity, response, or progression status) in patients treated at the MTD [ Designated as safety issue: No ]
- Relation of gene expression and polymorphisms to the intracellular content of pemetrexed disodium [ Designated as safety issue: No ]
- Response (complete and partial response, stable and progressive disease) in patients with measurable disease [ Designated as safety issue: No ]
- Response profile as measured by dose level and by primary disease site [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
See Detailed Description
Other Names:Drug: pemetrexed disodium
Other Names:Other: pharmacological study
Other Name: pharmacological studiesProcedure: ultrasound imaging
I. To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of PTK/ZK and pemetrexed disodium when given in combination.
II. To describe the toxicities associated with the combination of PTK/ZK with pemetrexed disodium.
III. To evaluate the pharmacokinetic interaction of combination of PTK/ZK with pemetrexed disodium at the MTD (Group II).
IV. To evaluate the intracellular content of pemetrexed disodium polyglutamates as a measure of activity of pemetrexed disodium transport and activation enzymes in the MTD expansion cohort (Group II).
V. To evaluate polymorphisms and gene expression of pemetrexed disodium target genes, and genes encoding enzymes involved in the transport, activation, and inactivation of pemetrexed disodium, and correlate haplotype-tagged SNPs or gene expression levels with intracellular levels of pemetrexed disodium polyglutamates, toxicity and/or efficacy or pemetrexed disodium in Group II.
VI. To evaluate pharmacogenetic, metabolic and clinical markers that may predict for hypertension induced by anti-VEGF therapy.
This is a dose-escalation study of vatalanib. Patients are assigned to 1 of 2 treatment groups.
GROUP I (dose escalation, closed to accrual 12/18/2007): Patients receive pemetrexed disodium IV over 10 minutes on day 1 and oral vatalanib twice daily on days 1-21.
GROUP II (MTD expansion group): Patients receive pemetrexed disodium IV on day 1, as in group I. Patients also receive oral vatalanib at the MTD twice daily on days 8-21 during course 1 and on days 1-21 during all subsequent courses.
In both groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00390000
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Julian Molina||Mayo Clinic|