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
18 Years
N/A
Both
Bladder Cancer, Brain and Central Nervous System Tumors, Breast Cancer, Esophageal Cancer, Extragonadal Germ Cell Tumor, Gastric Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) of lapatinib in course 1
Outcome Time Frame:
estimated to be 12 weeks
Safety Issue:
Yes
Principal Investigator
Mark M. Moasser, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Food and Drug Administration
Study ID:
UCSF CC#05591
NCT ID:
NCT00313599
Start Date:
February 2006
Completion Date:
December 2014
Related Keywords:
- Bladder Cancer
- Brain and Central Nervous System Tumors
- Breast Cancer
- Esophageal Cancer
- Extragonadal Germ Cell Tumor
- Gastric Cancer
- Lung Cancer
- Ovarian Cancer
- Prostate Cancer
- 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
- Urinary Bladder Neoplasms
- Breast Neoplasms
- Esophageal Diseases
- Esophageal Neoplasms
- Lung Neoplasms
- Stomach Neoplasms
- Nervous System Neoplasms
- Ovarian Neoplasms
- Prostatic Neoplasms
- Central Nervous System Neoplasms
- Neoplasms, Germ Cell and Embryonal
Name | Location |
|---|---|
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
