Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00313599
Recruitment Status : Completed
First Posted : April 12, 2006
Last Update Posted : July 2, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco

April 11, 2006
April 12, 2006
July 2, 2014
February 2006
December 2013   (Final data collection date for primary outcome measure)
Maximum tolerated dose (MTD) of lapatinib in course 1 [ Time Frame: estimated to be 12 weeks ]
Not Provided
Complete list of historical versions of study NCT00313599 on Archive Site
  • Toxicity [ Time Frame: up to 12 weeks ]
  • Anti-tumor efficacy and safety every 8 weeks [ Time Frame: until disease progression estimated to be 12 weeks ]
  • Pharmacokinetics during the first 2 weeks of treatment [ Time Frame: 2 weeks ]
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Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors
A Phase I Dose Escalation Study of a 2 Day Oral Lapatinib Chemosensitization Pulse Given Prior To Weekly Intravenous Abraxane™ in Patients With Advanced Solid Tumors

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.



  • 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.


  • 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.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Bladder Cancer
  • Brain and Central Nervous System Tumors
  • Breast Cancer
  • Esophageal Cancer
  • Extragonadal Germ Cell Tumor
  • Gastric Cancer
  • Lung Cancer
  • Ovarian Cancer
  • Prostate Cancer
  • Drug: lapatinib
    Other Names:
    • Tykerb
    • Tyverb
    • lapatinib ditosylate
  • Drug: paclitaxel
    Other Names:
    • paclitaxel albumin-stabilized nanoparticle formulation
    • Abraxane
    • Taxol
Experimental: 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.
  • Drug: lapatinib
  • Drug: paclitaxel
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
December 2013
December 2013   (Final data collection date for primary outcome measure)


  • 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


  • 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


  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
UCSF CC#05591
Not Provided
Not Provided
University of California, San Francisco
University of California, San Francisco
National Cancer Institute (NCI)
Study Chair: Mark M. Moasser, MD University of California, San Francisco
University of California, San Francisco
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP