Vinflunine and Erlotinib or Pemetrexed in Treating Patients With Unresectable or Metastatic Solid Tumors

NCT ID: NCT00320073

Last Updated: 2012-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2010-01-31

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Pemetrexed, Vinflunine, Folate, B12, Dexamethasone, Ondansetron, Midazolam

Group Type: EXPERIMENTAL

pemetrexed disodium

Intervention Type: DRUG

Pemetrexed is administered intravenously over 10 minutes, every 21 days

vinflunine

Intervention Type: DRUG

Vinflunine is administered intravenously over 20 minutes and should be given after pemetrexed, every 21 days

Arm B

Vinflunine, Erlotinib, Ondansetron, Midazolam

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

75 mg to 150mg

vinflunine

Intervention Type: DRUG

Vinflunine is administered intravenously over 20 minutes and should be given after pemetrexed, every 21 days

Interventions

erlotinib hydrochloride

75 mg to 150mg

Intervention Type: DRUG

pemetrexed disodium

Pemetrexed is administered intravenously over 10 minutes, every 21 days

Intervention Type: DRUG

vinflunine

Vinflunine is administered intravenously over 20 minutes and should be given after pemetrexed, every 21 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth C. Dees, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

CDR0000550148

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 0509

Identifier Type: -

Identifier Source: org_study_id