Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

July 1, 2014 updated by: University of California, San Francisco

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: paclitaxel
Other Names:
  • Taxol
  • Abraxane
  • paclitaxel albumin-stabilized nanoparticle formulation
Drug: lapatinib
Other Names:
  • Tykerb
  • Tyverb
  • lapatinib ditosylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) of lapatinib in course 1
Time Frame: estimated to be 12 weeks
estimated to be 12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Toxicity
Time Frame: up to 12 weeks
up to 12 weeks
Anti-tumor efficacy and safety every 8 weeks
Time Frame: until disease progression estimated to be 12 weeks
until disease progression estimated to be 12 weeks
Pharmacokinetics during the first 2 weeks of treatment
Time Frame: 2 weeks
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (ACTUAL)

December 1, 2013

Study Completion (ACTUAL)

December 1, 2013

Study Registration Dates

First Submitted

April 11, 2006

First Submitted That Met QC Criteria

April 11, 2006

First Posted (ESTIMATE)

April 12, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

July 2, 2014

Last Update Submitted That Met QC Criteria

July 1, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSF CC#05591

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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