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Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

Primary Purpose

Bladder Cancer, Brain and Central Nervous System Tumors, Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
lapatinib
paclitaxel
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lapatinib and Paclitaxel

Arm Description

Lapatinib will be self-administered orally on days 1 and 2 of weeks 1, 2, and 3 of a 4-week cycle. Lapatinib is the experimental therapy and is being administered using a dose escalation design guided by careful monitoring of toxicities. Abraxane will be administered IV weekly on day 3 of weeks 1, 2, and 3 of a 4-week cycle. Abraxane is being administered at the well tolerated and effective standard dose and schedule of 100mg/m2 weekly 3 out of 4 weeks as defined by previous phase I and II studies. Patients will continue on therapy as long as they are not experiencing toxicities and there is no evidence of disease progression.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of lapatinib in course 1

Secondary Outcome Measures

Toxicity
Anti-tumor efficacy and safety every 8 weeks
Pharmacokinetics during the first 2 weeks of treatment

Full Information

First Posted
April 11, 2006
Last Updated
July 1, 2014
Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00313599
Brief Title
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

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
February 2006 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lapatinib and Paclitaxel
Arm Type
Experimental
Arm Description
Lapatinib will be self-administered orally on days 1 and 2 of weeks 1, 2, and 3 of a 4-week cycle. Lapatinib is the experimental therapy and is being administered using a dose escalation design guided by careful monitoring of toxicities. Abraxane will be administered IV weekly on day 3 of weeks 1, 2, and 3 of a 4-week cycle. Abraxane is being administered at the well tolerated and effective standard dose and schedule of 100mg/m2 weekly 3 out of 4 weeks as defined by previous phase I and II studies. Patients will continue on therapy as long as they are not experiencing toxicities and there is no evidence of disease progression.
Intervention Type
Drug
Intervention Name(s)
lapatinib
Other Intervention Name(s)
Tykerb, Tyverb, lapatinib ditosylate
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
paclitaxel albumin-stabilized nanoparticle formulation, Abraxane, Taxol
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of lapatinib in course 1
Time Frame
estimated to be 12 weeks
Secondary Outcome Measure Information:
Title
Toxicity
Time Frame
up to 12 weeks
Title
Anti-tumor efficacy and safety every 8 weeks
Time Frame
until disease progression estimated to be 12 weeks
Title
Pharmacokinetics during the first 2 weeks of treatment
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark M. Moasser, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Chair
Facility Information:
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19706807
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.
Results Reference
result

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Lapatinib and Paclitaxel in Treating Patients With Advanced Solid Tumors

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