A Two Arm Phase I Dose Escalation Trial of Vinflunine With Erlotinib or Pemetrexed in Refractory Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Two Arm Phase I Dose Escalation Trial of Vinflunine With Erlotinib or Pemetrexed in Refractory Solid Tumors
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumors
- Advanced/unresectable or metastatic disease
- Refractory to standard therapy OR no standard therapy exists
- No lymphoma
- Measurable or evaluable disease
- Measurable disease is defined as at least one target lesion measuring ≥ 20 mm by
conventional techniques or ≥ 10 mm by spiral CT scan
- Evaluable disease includes ascites, pleural effusion, bone metastases, pulmonary
lymphangitic spread, and lesions not meeting above criteria as measurable
- Patients with clinically significant ascites or pleural effusions that
cannot be controlled by drainage are not eligible
- Brain metastases allowed if CNS-directed treatment has been given, patient has been
off CNS-directed therapy for > 3 months, and CNS disease has been clinically and
radiographically stable for at least 8 weeks
PATIENT CHARACTERISTICS:
- Life expectancy > 3 months
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Creatinine clearance ≥ 60 mL/min
- Patients assigned to group 1 with creatinine clearance 45-80 mL/min must be able
to withhold NSAIDS during pemetrexed disodium administration
- Total bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 3 times upper limit of normal (ULN) OR ≤ 5 times ULN if due to known
liver metastases
- No New York Heart Association class III or IV heart failure
- No unstable angina
- No myocardial infarction within the past 6 months
- No poorly controlled hypertension
- No prior allergic reaction to any vinca alkaloid
- No uncontrolled active infection or severe illness
- Able to receive vitamin B12 and folate supplementation and dexamethasone during
chemotherapy
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after last
dose of chemotherapy
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior chemotherapy, investigational agents, or surgery
- Concurrent cytochrome P450/CYP3A4 inducers or inhibitors are allowed provided patient
has been on a stable dose for ≥ 2 weeks prior to study entry
- No concurrent ketoconazole, itraconazole, ritonavir, amprenavir, or indinavir
- No concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (e.g., phenytoin,
carbamazepine, phenobarbital, primidone, or oxcarbazepine) for patients assigned to
group 2
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) of vinflunine and pemetrexed disodium
Outcome Description:
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
Outcome Time Frame:
1 year
Safety Issue:
Yes
Principal Investigator
Elizabeth C. Dees, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UNC Lineberger Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
LCCC 0509
NCT ID:
NCT00320073
Start Date:
August 2006
Completion Date:
January 2010
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
