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Phase I Study of Lapatinib (GW572016) in Combination With Weekly Ixabepilone (BMS 247550) in Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Study of Lapatinib (GW572016) in Combination With Weekly Ixabepilone (BMS 247550) in Advanced Solid Tumors



- To evaluate the safety and feasibility of lapatinib ditosylate in combination with
ixabepilone in patients with advanced solid tumors.


- To determine the maximum-tolerated dose of this regimen in these patients.

- To assess, preliminarily, the efficacy of this regimen in these patients.

- To perform laboratory correlative studies on tissue and blood specimens from these
patients to investigate potential predictors of response.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral lapatinib ditosylate once daily on days 1-28 and ixabepilone IV on
days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Archival tumor tissue samples are collected for EGFR/HER2 pathway analyses via
immunohistochemistry, mRNA analysis via RT-PCR, EGFR mutation analyses, Kras and braf
mutation analysis via sequencing, and RAS mutations via PCR and sequencing. Blood samples
are also collected periodically for tumor DNA and proteomics, acetylated alpha-tubulin
analysis, EGFR-HER2 pathway genotypes, and pharmacogenomics.

After completion of study therapy, patients are followed for 30 days.

Inclusion Criteria:

- Patients must have cytologically or histologically proven advanced solid tumors for
which there is no known standard therapy available or are not eligible for standard
therapy because of their performance status, or have progressed after standard

- Patients must have measurable or evaluable disease

- Patients must be 18 years of age or older

- Patients must have a Zubrod performance status of 0-2

- Patients must have an estimated survival of at least 3 months

- Any prior chemotherapy must have been completed at least 3 weeks prior to start of
this protocol and all side effects (except alopecia) resolved to grade 1 or less.
Any prior radiation must have been completed at least 2 weeks prior to start of
therapy. Patients must have completed prior trastuzumab (Herceptin) at least 4 weeks
prior to start of protocol therapy

- Patients must have adequate renal function

- Patients must have adequate liver function

- Patients must have a pretreatment granulocyte count of >1500/mm3 and platelet count
of >100 000/mm3.

- Patients must have a cardiac ejection fraction within the institutional range of
normal as measured by 2-D echocardiogram or MUGA scan.

- All patients must give informed consent

- Patients must be able to take and retain oral medication

- Patients of reproductive potential must agree to use an effective contraceptive
method while on treatment as the effects of these drugs on the unborn fetus are

Exclusion Criteria:

- Patients may not have previously received lapatinib, ixabepilone or any other
EGFR-TKI targeted agent. Prior trastuzumab (Herceptin) is allowed.

- Patients may not pregnant or breastfeeding as the effects of these drugs on the
unborn fetus are unknown.

- Patients with symptomatic brain metastasis or still requiring steroids and
anticonvulsants may not participate. Patients with asymptomatic treated brain
metastasis (surgical resection or radiotherapy) may be included if they are
neurologically stable and have been off steroids for at least 2 weeks.

- Patients with pre-existing neuropathy > grade 2 may not participate.

- Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements, will be excluded.

- History of other diseases, metabolic dysfunction, physical examination finding or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the patient at high risk from
treatment complications.

- Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for IV alimentation, or prior surgical procedures affecting absorption.

- HIV-positive patients receiving combination antiretroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with lapatinib.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.

- Patients requiring oral anticoagulants are eligible provided there is appropriate
close INR monitoring in place.

- Prior radiation must not have included more than 30% of bone marrow containing areas

- Any prior, severe history of hypersensitivity reaction to a drug formulated in

- Adherence to the requirements for concomitant medications classified as CYP3A4
inducers or inhibitors, or gastric pH modifiers

Type of Study:


Study Design:

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

Outcome Measure:

Safety and Toxicity

Outcome Description:

Assessed by NCI CTCAE v 3.0

Outcome Time Frame:

Toxicity will be assessed at the beginning of every cycle and on day 8 and 15 of every cycle for at least eight weeks (2 cycles). Maximum of 6 cycles.

Safety Issue:


Principal Investigator

Helen K. Chew, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Davis


United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

September 2011

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
University of California Davis Cancer CenterSacramento, California  95817
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Feist-Weiller Cancer Center at Louisiana State University Health SciencesShreveport, Louisiana  71130-3932