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| Sponsor: | GlaxoSmithKline |
|---|---|
| Information provided by: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT00619424 |
Purpose
This is an open-label, two-arm, Phase I, dose escalation study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) of pazopanib in combination with erlotinib (Arm A) or pazopanib in combination with pemetrexed (Arm B) in patients with advanced solid tumors. Patients will be enrolled in cohorts of 3 (in each arm) to receive escalating doses of pazopanib and erlotinib or pazopanib and pemetrexed. Dose escalation schemas for each study arm are described in the protocol. For each arm, the MTD regimen will be defined as the highest dose combination of the agents where no more than one out of six patients experiences a dose-limiting toxicity. Six to twelve additional patients in each arm will be studied with the MTD regimen to evaluate toxicity and pharmacokinetics. In arm A (erlotinib), a run-in phase with each drug separately will allow an evaluation of pharmacokinetics with each drug separately and also for the two drugs in combination. This will allow an assessment of potential drug-drug interactions. Pharmacokinetic endpoints will be AUC, Cmax, tmax and t1/2 of pazopanib, erlotinib, and pemetrexed, as well as pemetrexed clearance before and after administration of pazopanib in the extension cohort of Arm B. Antitumor activity will be assessed using RECIST criteria.
| Condition | Intervention | Phase |
|---|---|---|
|
Cancer Advanced Solid Tumours |
Drug: pazopanib Drug: erlotinib Drug: pemetrexed |
Phase I |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Study of Pazopanib in Combination With Either Erlotinib or Pemetrexed in Patients With Advanced Solid Tumors |
| Enrollment: | 58 |
| Study Start Date: | November 2007 |
| Study Completion Date: | September 2009 |
| Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
pazopanib + erlotinib: Experimental
Pazopanib and erlotinib are to be combined at different specified dose levels until an optimally tolerated dose level is identified. Pazopanib, a multi-targeted tyrosine kinase inhibitor of VEGFR-1, -2, and -3, PDGFR-alpha and beta, and c-kit and erlotinib, an epidermal growth factor (EGFR) inhibitor, are to be combined in an effort to simultaneously block two tightly woven cell signaling pathways.
|
Drug: pazopanib
Oral tablet administered daily in dosages of 400 - 800 mg.
Drug: erlotinib
oral tablet taken daily in dosages of 100-150 mg.
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pazopanib + pemetrexed: Experimental
Pazopanib and pemetrexed are to be combined at different specified dose levels until an optimally tolerated dose regimen is identified. Combination of an anti-VEGF therapy (such as bevacizumab) with systemic chemotherapy has demonstrated increased clinical efficacy in comparison with systemic chemotherapy alone in several malignancies. Hence, pazopanib, a multi-targeted tyrosine kinase inhibitor of VEGFR-1, -2, and -3, PDGFR-alpha and beta, and c-kit, was chosen to be combined with pemetrexed, a chemotherapeutic agent that inhibits the enzyme thymidylate synthase, in an effort to determine if an anti-angiogenesis inhibitor would enhance the activity of the approved chemotherapeutic agent pemetrexed.
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Drug: pazopanib
Oral tablet administered daily in dosages of 400 - 800 mg.
Drug: pemetrexed
IV chemotherapeutic agent administered every 21 days in dosages of 400-500 mg/m2
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
A subject will be considered eligible for inclusion in this study only if all of the following criteria are met:
Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up.
·Procedures conducted as a part of routine clinical management of the subject (e.g., blood count, imaging study) and obtained prior to signed informed consent may be utilized for Screening or Baseline purposes provided these tests are obtained as specified in the protocol.
Hematologic:
Absolute neutrophil count (ANC) ((≥1.5 X 10^9/L)) Hemoglobin (≥10 g/dL) Platelets (≥ 100 X 10^9/L) Prothrombin time (PT) or international normalized ration (INR) (≤ 1.2 X upper limit of normal (ULN)) Activated partial thromboplastin time (APTT) (≤ 1.2 X ULN)
Hepatic:
Total bilirubin (≤1.5 X ULN) AST and ALT (≤ 2.5 X ULN)
Renal:
Serum creatinine (≤ 1.5 mg/dL) Or, if greater than 1.5 mg/dL Calculated creatinine clearance (≤ 50 mL/min) Urine Protein to Creatinine Ratio (UPC)2 < 1
If UPC ≥ 1, then a 24-hour urine protein must be assessed and 24-hour urine protein must be <1 g protein to be eligible.
Note: Oral contraceptives are not reliable due to potential drug-drug interactions.
Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
A male with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.
Exclusion Criteria:
Contacts and Locations| United States, Colorado | |
| GSK Investigational Site | |
| Aurora, Colorado, United States, 80045 | |
| United States, New York | |
| GSK Investigational Site | |
| Buffalo, New York, United States, 14263 | |
| United States, Tennessee | |
| GSK Investigational Site | |
| Nashville, Tennessee, United States, 37203 | |
| Italy, Piemonte | |
| GSK Investigational Site | |
| Orbassano (to), Piemonte, Italy, 10043 | |
| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
More Information
| Responsible Party: | GSK ( Study Director ) |
| Study ID Numbers: | VEG109607 |
| Study First Received: | February 8, 2008 |
| Last Updated: | November 12, 2009 |
| ClinicalTrials.gov Identifier: | NCT00619424 History of Changes |
| Health Authority: | Italy: Isituto Superiore di Sanita'; United States: Food and Drug Administration; United States: Institutional Review Board |
|
Solid tumors pazopanib (GW786034) erlotinib pemetrexed |
anti-angiogenesis pharmacokinetics cytokine and angiogenic factors |
|
Antimetabolites Erlotinib Pemetrexed Neoplasms Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action |
Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors Folic Acid Antagonists Protein Kinase Inhibitors Pharmacologic Actions |