A Two Arm Phase I Dose Escalation Trial of Vinflunine With Erlotinib or Pemetrexed in Refractory Solid Tumors
- Define the maximum tolerated dose (MTD) of vinflunine and pemetrexed disodium in
patients with unresectable or metastatic solid tumors.
- Define the MTD of vinflunine and erlotinib hydrochloride in these patients.
- Determine the preliminary safety and efficacy (reported descriptively per patient
response; tumor specific response rate reported if applicable) of these regimens.
- Correlate CYP3A4 activity, as measured by midazolam clearance, with vinflunine plasma
OUTLINE: This is a nonrandomized, open-label, dose-escalation study. Patients are assigned
to 1 of 2 treatment groups.
- Group 1: Patients receive pemetrexed disodium IV over 10 minutes and vinflunine IV over
20 minutes on day 1.
Cohorts of 3-6 patients receive escalating doses of pemetrexed disodium and vinflunine until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional
patients may be treated at the MTD.
- Group 2: Patients receive vinflunine IV over 20 minutes on day 1 and oral erlotinib
hydrochloride once daily on days 2-21 of course 1 and on days 1-21 of all subsequent
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and vinflunine
until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3
or 2 of 6 patients experience dose-limiting toxicity. Additional patients may be treated at
In both groups, courses repeat every 21 days in the absence of unacceptable toxicity.
Blood samples are collected on day 1 of course 1 for pharmacodynamic studies.
After completion of study treatment, patients are followed for 30-40 days.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of vinflunine and pemetrexed disodium
The MTD is defined as the dose cohort where approximately 0.20 of patients experience DLT. Standard "groups of three" phase I dose escalation design will be used in each arm. Each dose cohort will accrue a minimum of three patients.The estimated MTD is the dose level below the dose that induced dose limiting toxicity (DLT) in one third or more of patients
Elizabeth C. Dees, MD
UNC Lineberger Comprehensive Cancer Center
United States: Food and Drug Administration
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