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

NCT00320073 | Completed Phase 1 DMC

• 2 other identifiers: LCCC 0509CDR0000550148
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (3)

• 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

  1 year

• Maximum tolerated dose (MTD) of vinflunine and continuously dosed erlotinib

  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

  1 year

• Maximum tolerated dose (MTD) of vinflunine and intermittently dosed erlotinib

  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

  1 year

Study Arms (2)

Arm A

EXPERIMENTAL

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

Drug: pemetrexed disodium; Drug: vinflunine

Arm B

EXPERIMENTAL

Vinflunine, Erlotinib, Ondansetron, Midazolam

Drug: erlotinib hydrochloride; Drug: vinflunine

Interventions

erlotinib hydrochloride DRUG

75 mg to 150mg

Arm B

pemetrexed disodium DRUG

Pemetrexed is administered intravenously over 10 minutes, every 21 days

Arm A

vinflunine DRUG

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

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

MeSH Terms

Interventions

Erlotinib Hydrochloride; Pemetrexed; vinflunine

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Elizabeth C. Dees, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2006
• First Posted: May 3, 2006
• Study Start: August 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: January 1, 2010
• Last Updated: May 16, 2012

Record last verified: 2012-05

Locations

US (1)