Know Cancer

forgot password

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

Phase 1
18 Years
Open (Enrolling)
Bladder Cancer, Brain and Central Nervous System Tumors, Breast Cancer, Esophageal Cancer, Extragonadal Germ Cell Tumor, Gastric Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer

Thank you

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



- 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.


- 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


- 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


- 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

- 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


- 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

- 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:


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:


Principal Investigator

Mark M. Moasser, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:

UCSF CC#05591



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



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