Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00313599

Last Updated: 2014-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2013-12-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may help paclitaxel work better by making tumor cells more sensitive to the drug. Lapatinib may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving lapatinib together with paclitaxel may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with paclitaxel in treating patients with advanced solid tumors.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of a 2-day pulse of lapatinib that can be given prior to paclitaxel (albumin-stabilized nanoparticle formulation ) (ABI-007; Abraxane™) in patients with advanced solid tumor malignancies.

Secondary

• Define the toxicity of this regimen.
• Determine, preliminarily, the antitumor efficacy and safety of ABI-007 when preceded by a 2-day pulse of lapatinib.
• Characterize the potential of the molecular markers within circulating tumor cells as markers of response (e.g., HER2 and AKT) or apoptotic markers.
• Determine whether lapatinib given at MTD prior to ABI-007 alters the pharmacokinetic properties of the paclitaxel component of ABI-007.

OUTLINE: This is a does-escalation study of lapatinib. Patients are stratified according to dose level.

Patients receive oral lapatinib on days 1, 2, 8, 9, 15, and 16 and paclitaxel (albumin-stabilized nanoparticle formulation) (ABI-007; Abraxane™) IV over 30 minutes on days 3, 10, and 17. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of lapatinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicities.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Conditions

Bladder Cancer; Brain and Central Nervous System Tumors; Breast Cancer; Esophageal Cancer; Extragonadal Germ Cell Tumor; Gastric Cancer; Lung Cancer; Ovarian Cancer; Prostate Cancer

Study Design

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

Study Groups

Lapatinib and Paclitaxel

Lapatinib will be self-administered orally on days 1 and 2 of weeks 1, 2, and 3 of a 4-week cycle. Lapatinib is the experimental therapy and is being administered using a dose escalation design guided by careful monitoring of toxicities. Abraxane will be administered IV weekly on day 3 of weeks 1, 2, and 3 of a 4-week cycle. Abraxane is being administered at the well tolerated and effective standard dose and schedule of 100mg/m2 weekly 3 out of 4 weeks as defined by previous phase I and II studies. Patients will continue on therapy as long as they are not experiencing toxicities and there is no evidence of disease progression.

Group Type: EXPERIMENTAL

lapatinib

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Interventions

lapatinib

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Other Intervention Names

Tykerb; Tyverb; lapatinib ditosylate; paclitaxel albumin-stabilized nanoparticle formulation; Abraxane; Taxol

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor, including the following tumor types:

• Breast cancer
• Non-small cell lung cancer
• Prostate cancer
• Bladder cancer
• Gastroesophageal junction cancer
• Ovarian cancer
• Germ cell tumor
• Advanced or metastatic disease
• No effective curative therapy exists
• Evaluable disease

• Measurable disease not required
• Bone-only disease allowed
• No progressing brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Creatinine normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious intercurrent medical or psychiatric illness
• No serious active infection
• No gastrointestinal tract disease that would impair a patient's ability to take oral medication
• No history of significant cardiac disease, including any of the following:

• Congestive heart failure
• Symptomatic cardiac arrhythmias
• Unstable angina
• No pre-existing peripheral neuropathy ≥ 2

PRIOR CONCURRENT THERAPY:

• Any number of prior therapies allowed
• Prior paclitaxel, tyrosine kinase inhibitor therapy, or endothelial growth factor inhibitors allowed
• At least 14 days since prior and no concurrent CYP3A4 inducers or herbal or dietary supplements
• At least 7 days since prior and no concurrent CYP3A4 inhibitors
• At least 6 months since prior and no concurrent amiodarone
• More than 1 month since prior chemotherapy, radiotherapy, hormonal therapy, or investigational anticancer agents
• Concurrent continued use of gonadal suppression agents (i.e., goserelin acetate or leuprolide acetate) allowed
• No antacids 1 hour before and after study drug administration
• No concurrent retinoids
• No concurrent hormonal anticancer agent
• No other concurrent anticancer chemotherapy or investigational anticancer agents

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark M. Moasser, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Countries

United States

References

Chien AJ, Illi JA, Ko AH, Korn WM, Fong L, Chen LM, Kashani-Sabet M, Ryan CJ, Rosenberg JE, Dubey S, Small EJ, Jahan TM, Hylton NM, Yeh BM, Huang Y, Koch KM, Moasser MM. A phase I study of a 2-day lapatinib chemosensitization pulse preceding nanoparticle albumin-bound Paclitaxel for advanced solid malignancies. Clin Cancer Res. 2009 Sep 1;15(17):5569-75. doi: 10.1158/1078-0432.CCR-09-0522. Epub 2009 Aug 25.

Reference Type: RESULT

PMID: 19706807 (View on PubMed)

Other Identifiers

UCSF CC#05591

Identifier Type: -

Identifier Source: org_study_id