Clinical trial NCT00447226: Randomized Discontinuation Study of Lapatinib Versus Placebo in Subjects With Documented Tumor Progression After Chemotherapy, or Where no Approved Therapy Exists
Official title: A Phase II, Placebo Controlled, Double-Blind, Randomized, Discontinuation Study of Lapatinib Administered Orally to Subjects With ErbB2 Positive Ovarian, Gastric/Esophageal Adenocarcinoma, Uterine Serous Papillary, or Bladder Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cancer
Keywords: Ovarian Cancer
Bladder Cancer
ErbB2 positive
Lapatinib
Gastric/Esophageal Cancer
Uterine Serous Papillary Cancer
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-03-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will examine the efficacy and safety of lapatinib in patients with ErbB2 positive ovarian, gastric/esophageal adenocarcinoma, uterine serous papillary, or bladder cancers.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent.
* Age \>= 18 years old.
* Life expectancy of at least 12 weeks.
* Have histologically confirmed ovarian, gastric/esophageal adenocarcinoma, uterine serous papillary, or bladder cancer.
* Have ErbB2-positive cancer as determined by Fluorescence In Situ Hybridization (FISH) assay.
* Have documented tumor progression after receiving all standard/approved chemotherapies per National Comprehensive Cancer Network (NCCN) guidelines (V1) for their specific cancer and no approved therapy exists.
* Have one or more tumors measurable by medical imaging and assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Have archived tumor tissue available for biomarker analysis.
* Have a negative serum pregnancy test if female of childbearing potential.
* Any chemotherapy, major surgery, or irradiation must have been completed at least 3 weeks prior to receiving study drug (6 weeks for mitomycin-C or nitrosourea) and subject must have recovered from all toxicities incurred as a result of previous therapy.
* Have a gastrointestinal tract intact enough to swallow and assure absorption of the drug.
* Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (for example, intrauterine device, birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product. Males able to father a child must practice adequate methods of birth control or practice complete abstinence from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment.
* Have a cardiac ejection fraction within institutional range of normal as measured by either echocardiogram or multigated acquisition scans. The same method of cardiac evaluation must be used consistently throughout the study.
* Subjects must have adequate organ function:

Hematologic:

absolute neutrophil count \>1.5 x 109/L hemoglobin \>9 g/dL platelets \>75 x 109/L

Hepatic:

albumin \>2.5 g/dL serum bilirubin \<1.25 x upper limit of normal aspartate aminotransferase/alanine aminotransferase \<3 x ULN if no documented liver metastases aspartate aminotransferase/alanine aminotransferase \<5 x ULN with documented liver metastases

Renal:

serum creatinine \<2.0 mg/dL

* OR - calculated creatinine clearance1 \>40 mL/min

Exclusion Criteria:

* Have New York Heart Association Class III or IV, cardiac disease, myocardial infarction within past 6 months, unstable arrhythmia or evidence of ischemia on electrocardiogram.
* Subjects who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
* Concurrent treatment with an investigational agent or participation in another treatment clinical trial.
* Prior lapatinib therapy.
* ECOG Performance Status 2 or greater.
* Subjects receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer. Concurrent treatment with bisphosphonates is allowed.
* History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib.
* Concurrent treatment with prohibited medications.
* Malabsorption syndrome, resection of the small bowel or active, uncontrolled ulcerative colitis.
* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety.
* Uncontrolled infection.
* Pregnant or lactating females.

Primary outcomes:
measure: Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose
timeFrame: Week 12
measure: Percentage of Participants Who Remained Progression-free 12 Weeks After Randomization
timeFrame: Week 12 after randomization.
Secondary outcomes:
measure: Duration of Response
timeFrame: (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib)
measure: Progression-free Survival (PFS)
timeFrame: From start of treatment to disease progression/death (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib)
measure: Time to Disease Progression (TTP)
timeFrame: From start of treatment to disease progression/death (up to 83.3 weeks)
measure: Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1
timeFrame: Pre-dose and every 6 weeks until withdrawal (up to 84.1 weeks)
measure: Incidence of MET Amplification in Gastric Cancer
timeFrame: Performed on archived tissue collected at screening.
measure: Incidence of ErbB2-positive Participants
timeFrame: Screening
Other outcomes:
Locations:
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Bedford
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Tyler
country: United States
facility: GSK Investigational Site
state: Texas
city: Webster
country: United States
facility: GSK Investigational Site
state: Texas
city: Leesburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Newport News
country: United States
facility: GSK Investigational Site
state: Virginia
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Vancouver
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Galsky MD, Von Hoff DD, Neubauer M, Anderson T, Fleming M, Nagarwala Y, Mahoney JM, Midwinter D, Vocila L, Zaks TZ. Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. Invest New Drugs. 2012 Apr;30(2):695-701. doi: 10.1007/s10637-010-9541-0. Epub 2010 Sep 22.