Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00313599
• Other study ID #: UCSF CC#05591
• Status: Completed
• Phase: Phase 1
• First received: April 11, 2006
• Last updated: July 1, 2014
• Start date: February 2006
• Est. completion date: December 2013

Study information

• Verified date: July 2014
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Brain and Central Nervous System Tumors
• Breast Cancer
• Central Nervous System Neoplasms
• Esophageal Cancer
• Esophageal Neoplasms
• Extragonadal Germ Cell Tumor
• Gastric Cancer
• Lung Cancer
• Neoplasms
• Nervous System Neoplasms
• Ovarian Cancer
• Prostate Cancer
• Prostatic Neoplasms
• Stomach Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• lapatinib

• paclitaxel

Locations

Country	Name	City	State
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of lapatinib in course 1		estimated to be 12 weeks	Yes
Secondary	Toxicity		up to 12 weeks	Yes
Secondary	Anti-tumor efficacy and safety every 8 weeks		until disease progression estimated to be 12 weeks	Yes
Secondary	Pharmacokinetics during the first 2 weeks of treatment		2 weeks	Yes