Clinical trial NCT00313599: Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bladder Cancer
Brain and Central Nervous System Tumors
Breast Cancer
Esophageal Cancer
Extragonadal Germ Cell Tumor
Gastric Cancer
Lung Cancer
Ovarian Cancer
Prostate Cancer
Keywords: 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
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-12
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of lapatinib in course 1
timeFrame: estimated to be 12 weeks
Secondary outcomes:
measure: Toxicity
timeFrame: up to 12 weeks
measure: Anti-tumor efficacy and safety every 8 weeks
timeFrame: until disease progression estimated to be 12 weeks
measure: Pharmacokinetics during the first 2 weeks of treatment
timeFrame: 2 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Mark M. Moasser, MD
role: STUDY_CHAIR
References:
citation: 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.