Vinflunine and Erlotinib or Pemetrexed in Treating Patients With Unresectable or Metastatic Solid Tumors
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Registration Number
- NCT00320073
- Lead Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as vinflunine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib and pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vinflunine together with erlotinib or pemetrexed may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vinflunine when given together with erlotinib or pemetrexed in treating patients with unresectable or metastatic solid tumors.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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 clearance.
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 courses.
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 the MTD.
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm A pemetrexed disodium Pemetrexed, Vinflunine, Folate, B12, Dexamethasone, Ondansetron, Midazolam Arm B erlotinib hydrochloride Vinflunine, Erlotinib, Ondansetron, Midazolam Arm B vinflunine Vinflunine, Erlotinib, Ondansetron, Midazolam Arm A vinflunine Pemetrexed, Vinflunine, Folate, B12, Dexamethasone, Ondansetron, Midazolam
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) of vinflunine and pemetrexed disodium 1 year 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
Maximum tolerated dose (MTD) of vinflunine and continuously dosed erlotinib 1 year 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
Maximum tolerated dose (MTD) of vinflunine and intermittently dosed erlotinib 1 year 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States