A Phase I Study Of Pazopanib With Either Erlotinib Or Pemetrexed In Patients With Advanced Solid Tumors

Conditions

• Lung Cancer, Non-Small Cell

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• pazopanib — DRUG
  Oral tablet administered daily in dosages of 400 - 800 mg.
• erlotinib — DRUG
  oral tablet taken daily in dosages of 100-150 mg.
• pemetrexed — DRUG
  IV chemotherapeutic agent administered every 21 days in dosages of 400-500 mg/m2

Study Details

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.

Key Dates

First listed

Feb 21, 2008

Start date

Nov 15, 2007

Status verified

Nov 2017

Primary completion

Sep 4, 2009

Completion

Sep 4, 2009

Study Design

Enrollment

58 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: pazopanib + erlotinib
  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.
• Experimental: pazopanib + pemetrexed
  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.

Primary Outcome Measure

MTD regimen for each combination regimen in each arm of the study as determined by an evaluation of AEs and changes in laboratory values. The MTD = highest dosing regimen that results in dose limiting toxicity in <= 1 of 6 patients. [ Time Frame: Through a minimum of two cycles of therapy for each subject ]

Locations (3)

Find similar trials in Aurora, CO

Related Studies

• A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs
  PHASE1/PHASE2 · Recruiting · Krystal Biotech, Inc. · Dothan, Alabama
• Engagement of Veterans With Lung Cancer
  Recruiting · Palo Alto Veterans Institute for Research · Palo Alto, California