Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsors and Collaborators:	UCSF Helen Diller Family Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00313599

Purpose

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.

Condition	Intervention	Phase
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 ditosylate Drug: paclitaxel albumin-stabilized nanoparticle formulation	Phase I

Genetics Home Reference related topics: bladder cancer breast cancer

MedlinePlus related topics: Bladder Cancer Breast Cancer Cancer Esophageal Cancer Esophagus Disorders Lung Cancer Ovarian Cancer Prostate Cancer Stomach Cancer

Drug Information available for: Paclitaxel Lapatinib Lapatinib Ditosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose (MTD) of lapatinib in course 1 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Anti-tumor efficacy and safety every 8 weeks [ Designated as safety issue: Yes ]
Presence of molecular markers as markers of response (e.g., HER2, AKT, and apoptotic markers) in circulating tumor cells on days 1, 2, and 3 of course 1 [ Designated as safety issue: No ]
Pharmacokinetics at the MTD during the first 2 weeks of treatment [ Designated as safety issue: Yes ]

Estimated Enrollment:	15
Study Start Date:	February 2006
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313599

Locations

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

Sponsors and Collaborators

UCSF Helen Diller Family Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Mark M. Moasser, MD

UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000471230, UCSF-05991, UCSF-H47800-27167-01
Study First Received:	April 11, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00313599
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent breast cancer
stage IV breast cancer
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent prostate cancer
stage IV prostate cancer
recurrent bladder cancer
stage IV bladder cancer
recurrent gastric cancer
stage IV gastric cancer
recurrent esophageal cancer
stage IV esophageal cancer
recurrent ovarian germ cell tumor
stage IV ovarian germ cell tumor

adult central nervous system germ cell tumor
ovarian choriocarcinoma
ovarian dysgerminoma
ovarian embryonal carcinoma
ovarian yolk sac tumor
ovarian mixed germ cell tumor
recurrent ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent extragonadal non-seminomatous germ cell tumor
recurrent extragonadal seminoma
stage IV extragonadal non-seminomatous germ cell tumor
stage IV extragonadal seminoma
recurrent extragonadal germ cell tumor

Study placed in the following topic categories:

Thoracic Neoplasms
Prostatic Diseases
Seminoma
Urogenital Neoplasms
Nonseminomatous germ cell tumor
Central Nervous System Neoplasms
Urologic Neoplasms
Ovarian epithelial cancer
Lung Neoplasms
Breast Diseases
Nervous System Neoplasms
Endocrine Gland Neoplasms
Non-small cell lung cancer
Digestive System Neoplasms
Urinary Bladder Diseases

Urinary Bladder Neoplasms
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Stomach cancer
Genital Diseases, Male
Carcinoma
Paclitaxel
Lung Diseases
Gastrointestinal Neoplasms
Esophageal Diseases
Prostatic Neoplasms
Carcinoma, Non-Small-Cell Lung
Genital Neoplasms, Male
Gastrointestinal Diseases

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents

Protein Kinase Inhibitors
Pharmacologic Actions
Adnexal Diseases
Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009