Lapatinib and Vinorelbine in Treating Patients With Advanced Solid Tumors

NCT00389922 | Completed Phase 1 DMC

• 5 other identifiers: CDR0000505878P30CA093373UCDCC-171UCDCC-200513681-1GSK-104241
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with vinorelbine may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with vinorelbine in treating patients with advanced solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Toxicity as assessed by NCI CTCAE v3.0

  Completion of study

Secondary Outcomes (6)

• Maximum tolerated dose of lapatinib ditosylate when administered with vinorelbine ditartrate as assessed by NCI CTCAE v3.0

  Completion of study

• Response rate (complete response, partial response, progressive disease, and stable disease) assessed at baseline and prior to courses 3 and 5

  Completion of study

• Best response

  Completion of study

• Survival

  Completion of study

• Progression-free survival

  Completion of study

Study Arms (2)

A (Daily Dosing)

EXPERIMENTAL

Oral lapatinib given daily for 28 days plus IV vinorelbine given weekly (3 out of 4 weeks) Cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate 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 during course 1. At least 6 patients are treated at the MTD. Once the MTD of lapatinib has been determined, patients may be accrued to group B or to a separate pharmacokinetics cohort in group A.

Drug: lapatinib ditosylate; Drug: vinorelbine ditartrate; Genetic: comparative genomic hybridization; Genetic: cytogenetic analysis; Genetic: gene expression analysis; Genetic: mutation analysis; Genetic: polymerase chain reaction; Genetic: polymorphism analysis; Genetic: proteomic profiling; Genetic: reverse transcriptase-polymerase chain reaction; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

B (Intermittent Dosing)

EXPERIMENTAL

Oral lapatinib given days 2-5, 9-12 and 16-25 plus IV vinorelbine given weekly (3 out of 4 weeks) Cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate 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 during course 1. At least 6 patients are treated at the MTD. Once the MTD of lapatinib has been determined, patients may be accrued to group B or to a separate pharmacokinetics cohort in group A.

Drug: lapatinib ditosylate; Drug: Vinorelbine ditartrate

Interventions

lapatinib ditosylate DRUG

Given orally for 28 days per dose level (Dose level 1: 250mg; Dose level 2: 500mg; Dose level 3: 1000mg; Dose level 4: 1250mg; Dose level 5: 1500mg; Dose level 6: 1500mg)

Also known as: Tykerb

A (Daily Dosing)

Vinorelbine ditartrate DRUG

Given IV Days 1, 8 and 15 per dose level (Dose level 1: 20mg/m2; Dose level 2: 20mg/m2; Dose level 3: 20mg/m2; Dose level 4: 20mg/m2; Dose level 5: 20mg/m2; Dose level 6: 25mg/m2)

Also known as: Navelbine

A (Daily Dosing)

comparative genomic hybridization GENETIC

Molecular correlative study

A (Daily Dosing)

cytogenetic analysis GENETIC

Molecular correlative study

A (Daily Dosing)

gene expression analysis GENETIC

Molecular correlative study

A (Daily Dosing)

mutation analysis GENETIC

Molecular correlative study

A (Daily Dosing)

polymerase chain reaction GENETIC

Molecular correlative study

A (Daily Dosing)

polymorphism analysis GENETIC

Molecular correlative study

A (Daily Dosing)

proteomic profiling GENETIC

Molecular correlative study

A (Daily Dosing)

reverse transcriptase-polymerase chain reaction GENETIC

Molecular correlative study

A (Daily Dosing)

immunohistochemistry staining method OTHER

Molecular correlative study

A (Daily Dosing)

laboratory biomarker analysis OTHER

Molecular correlative study

A (Daily Dosing)

Eligibility Criteria

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

You may qualify if:

• Cytologically or histologically proven advanced solid tumors for which there is no known standard therapy available or are not eligible for standard therapy because of their performance status, or have progressed after no more than 2 prior chemotherapy regimens for metastatic disease.
• Measurable or evaluable disease. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy.
• years of age or older.
• Zubrod performance status of 0-2.
• Estimated survival of at least 3 months.
• Any prior chemotherapy must have been completed at least 4 weeks prior to start of this protocol and all side effects (except alopecia) resolved to grade 1 or less. Any prior radiation must have been completed at least 2 weeks prior to start of therapy. For prior mitomycin chemotherapy a 6-week interval is required. Patients must have completed prior trastuzumab at least 4 weeks prior to start of protocol therapy.
• Adequate renal function
• Adequate liver function
• Pretreatment granulocyte count of \>1500/mm3 and platelet count of \>100 000/mm3.
• Cardiac ejection fraction within the institutional range of normal as measured by 2-D echocardiogram or MUGA scan.
• Asymptomatic treated brain metastasis may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 4 weeks.
• All patients must give informed consent.
• Able to take and retain oral medication.
• Patients of reproductive potential must agree to use an effective contraceptive method

You may not qualify if:

• Patients may not have previously received lapatinib, vinorelbine or any other EGFR-1 targeted agent. Prior trastuzumab is allowed.
• Females cannot be pregnant or breastfeeding
• Symptomatic brain metastasis or still requiring steroids and anticonvulsants may not participate.
• Pre-existing neuropathy \> grade 2 may not participate.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, will be excluded.
• History of other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications.
• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib.
• Patients requiring oral anticoagulants are eligible provided there is appropriate close INR monitoring is in place. If medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with lapatinib is not expected.
• Adherence to the requirements for concomitant medications classified as CYP3A4 inducers or inhibitors, or gastric pH modifiers

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

MeSH Terms

Interventions

Lapatinib; Vinorelbine; Comparative Genomic Hybridization; Cytogenetic Analysis; Gene Expression Profiling; Polymerase Chain Reaction; Amplified Fragment Length Polymorphism Analysis; Reverse Transcriptase Polymerase Chain Reaction; Immunohistochemistry

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Genetic Techniques; Investigative Techniques; Molecular Diagnostic Techniques; Nucleic Acid Hybridization; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Nucleic Acid Amplification Techniques; DNA Fingerprinting; Histocytochemistry; Histological Techniques; Immunologic Techniques

Study Officials

• Helen K. Chew, MD

  University of California, Davis

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: December 1, 2005
• Primary Completion: April 1, 2009
• Study Completion: December 1, 2011
• Last Updated: April 19, 2012

Record last verified: 2012-04

Locations

US (4)