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Sponsored by: |
GlaxoSmithKline |
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Information provided by: | GlaxoSmithKline |
ClinicalTrials.gov Identifier: | NCT00619424 |
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 |
Drug: Pazopanib (GW786034) |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Pharmacokinetics/Dynamics Study |
Official Title: | A Phase I Study of Pazopanib in Combination With Either Erlotinib or Pemetrexed in Patients With Advanced Solid Tumors |
Estimated Enrollment: | 55 |
Study Start Date: | November 2007 |
Estimated Study Completion Date: | September 2008 |
Estimated Primary Completion Date: | September 2008 (Final data collection date for primary outcome measure) |
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.
Hematologic:
Absolute neutrophil count (ANC) ((≥1.5 X 10^9/L)) Hemoglobin1 (≥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.
A female subject is eligible to enter and participate in the study if she is of: • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any woman who has had:• A hysterectomy
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.
For Arm B (pemetrexed plus pazopanib) subjects:
Exclusion Criteria:
Clinically significant gastrointestinal abnormalities which might interfere with oral dosing, including but not limited to:
History of any one of more of the following cardiovascular conditions within the past 6 months:
Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 24 hours. The mean SBP / DBP values from each blood pressure assessment must be < 140/90mmHg in order for a subject to be eligible for the study. See Section 4.3.4 Dose Modifications, Section 6.3.2 Vital Signs and Blood Pressure Monitoring for details on blood pressure control and reassessment prior to study enrollment.
Note: Subjects with recent DVT who have been treated with therapeutic anti coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible. As noted in Section 8.2, use of therapeutic levels of warfarin must have ended more than 14 days prior to first dose of study drug.
Contact: US GSK Clinical Trials Call Center | 877-379-3718 |
United States, Colorado | |
GSK Investigational Site | Recruiting |
Aurora, Colorado, United States, 80045 | |
United States, New York | |
GSK Investigational Site | Recruiting |
Buffalo, New York, United States, 14263 | |
United States, Tennessee | |
GSK Investigational Site | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Italy, Piemonte | |
GSK Investigational Site | Recruiting |
Orbassano (TO), Piemonte, Italy, 10043 |
Study Director: | GSK Clinical Trials, MD | GlaxoSmithKline |
Responsible Party: | GSK ( Study Director ) |
Study ID Numbers: | VEG109607 |
Study First Received: | February 8, 2008 |
Last Updated: | December 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00619424 History of Changes |
Health Authority: | United States: Institutional Review Board |
Solid tumors pazopanib (GW786034) erlotinib |
pemetrexed anti-angiogenesis pharmacokinetics |
Antimetabolites Folic Acid Erlotinib |
Pemetrexed Folic Acid Antagonists Protein Kinase Inhibitors |
Antimetabolites Erlotinib Pemetrexed Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |
Therapeutic Uses Enzyme Inhibitors Folic Acid Antagonists Protein Kinase Inhibitors Pharmacologic Actions |