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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00320073
First received: April 27, 2006
Last updated: May 14, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: erlotinib hydrochloride
Drug: pemetrexed disodium
Drug: vinflunine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Arm Phase I Dose Escalation Trial of Vinflunine With Erlotinib or Pemetrexed in Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of vinflunine and pemetrexed disodium [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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


Enrollment: 41
Study Start Date: August 2006
Study Completion Date: January 2010
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Pemetrexed, Vinflunine, Folate, B12, Dexamethasone, Ondansetron, Midazolam
Drug: pemetrexed disodium
Pemetrexed is administered intravenously over 10 minutes, every 21 days
Drug: vinflunine
Vinflunine is administered intravenously over 20 minutes and should be given after pemetrexed, every 21 days
Experimental: Arm B
Vinflunine, Erlotinib, Ondansetron, Midazolam
Drug: erlotinib hydrochloride
75 mg to 150mg
Drug: vinflunine
Vinflunine is administered intravenously over 20 minutes and should be given after pemetrexed, every 21 days

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00320073

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Elizabeth C. Dees, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00320073     History of Changes
Other Study ID Numbers: LCCC 0509, CDR0000550148
Study First Received: April 27, 2006
Last Updated: May 14, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Pemetrexed
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014