Randomized Discontinuation Study of Lapatinib Versus Placebo in Subjects With Documented Tumor Progression After Chemotherapy, or Where no Approved Therapy Exists

This study has been terminated.
(The study had failed to meet the primary objective of tumor response rate at 12 weeks from first dose.)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00447226
First received: March 13, 2007
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: Oral lapatinib tablets or placebo tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria In Solid Tumors (RECIST): Complete response (CR), disappearance of all lesions; partial response (PR), >=30% decrease in the measurements of the largest lesions; stable disease (SD), insufficient shrinkage to qualify for PR or insufficient increase to qualify for progressive disease (PD); PD, >=20% increase in measurements of lesions or appearance of new lesions. Data were not fully analyzed due to early study termination.

  • Percentage of Participants Who Remained Progression-free 12 Weeks After Randomization [ Time Frame: Week 12 after randomization. ] [ Designated as safety issue: No ]
    The percentage of participants who did not show signs of progressive disease 12 weeks after receiving lapatinib or placebo in Stage 2 of the study (participants who maintained SD in Stage 1 were randomized to either lapatinib or placebo) was measured. Formal statistics for treatment comparison were not performed, due to early study termination. The percentage of participants displayed below includes those with CR + PR + SD.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib) ] [ Designated as safety issue: No ]
    Duration of response was calculated as the time from first documented partial response (PR; >=30% decrease in the measurements of the largest lesions) or complete response (CR; disappearance of all lesions) until disease progression, the time when the participant began a new anti-cancer therapy, or death. Data were not analyzed due to early study termination.

  • Progression-free Survival (PFS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Progression-free survival was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored". Data were not analyzed due to early study termination.

  • Time to Disease Progression (TTP) [ Time Frame: From start of treatment to disease progression/death (up to 83.3 weeks) ] [ Designated as safety issue: No ]
    Time to disease progression was calculated as the time from the start of treatment to disease progression or death due to disease progression. For participants who did not progress, the date of last contact was used and for those who died due to other causes, the date of death was used. The word used for such participants was "censored". As the median value in the placebo arm was not reached (2 participants were censored and 2 were ongoing), results for the placebo arm are not displayed in the table below.

  • Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1 [ Time Frame: Pre-dose and every 6 weeks until withdrawal (up to 84.1 weeks) ] [ Designated as safety issue: No ]
    CA-125 is a "tumor marker", found in greater concentration in tumor cells than other cells of the body. In particular, CA-125 is present in greater concentration in ovarian cancer cells than in other cells. A decreasing level generally indicates that therapy has been effective, whereas an increasing level indicates tumor recurrence.

  • Incidence of MET Amplification in Gastric Cancer [ Time Frame: Performed on archived tissue collected at screening. ] [ Designated as safety issue: No ]
    The number of gastric cancer participants with MET amplification (determined by fluorescence in situ hybridization [FISH] assay) compared to the total number of gastric cancer participants screened was to be recorded. Amplification of the MET gene has been reported to be related to carcinogenesis, progression of gastric cancer, and poor prognosis. Data were not analyzed due to early study termination.

  • Incidence of ErbB2-positive Participants [ Time Frame: Screening ] [ Designated as safety issue: No ]
    The number of ErbB2-positive participants (determined by FISH assay) compared to the total number of participants screened was to be recorded. Over-expression of ErbB2 has been correlated with an overall poor prognosis. Data were not analyzed, due to early study termination.


Enrollment: 32
Study Start Date: May 2007
Study Completion Date: September 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib Oral Tablets Drug: Oral lapatinib tablets or placebo tablets
Subjects administered open label lapatinib, 1500 mg to be taken orally once a day, for 12 weeks. After 12 weeks, subjects with a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) will continue to receive open label lapatinib (1500 mg/day orally) until disease progression. Subjects who maintain stable disease will be randomized in a 1:1 ratio to enter stage 2 of the study and receive double blind therapy of either lapatinib 1500 mg/day orally or placebo. Subjects who progress on placebo will have the option to receive lapatinib 1500 mg/day orally until further progression. Those who progress on lapatinib will be withdrawn from the study.
Other Name: Oral lapatinib tablets or placebo tablets
Placebo Comparator: Placebo Control Drug: Oral lapatinib tablets or placebo tablets
Subjects administered open label lapatinib, 1500 mg to be taken orally once a day, for 12 weeks. After 12 weeks, subjects with a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) will continue to receive open label lapatinib (1500 mg/day orally) until disease progression. Subjects who maintain stable disease will be randomized in a 1:1 ratio to enter stage 2 of the study and receive double blind therapy of either lapatinib 1500 mg/day orally or placebo. Subjects who progress on placebo will have the option to receive lapatinib 1500 mg/day orally until further progression. Those who progress on lapatinib will be withdrawn from the study.
Other Name: Oral lapatinib tablets or placebo tablets

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447226

Locations
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80218
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46219
United States, Kansas
GSK Investigational Site
Overland Park, Kansas, United States, 66210
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
United States, Missouri
GSK Investigational Site
St. Louis, Missouri, United States, 63141
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89109
United States, New York
GSK Investigational Site
Albany, New York, United States, 12206
United States, North Carolina
GSK Investigational Site
Raleigh, North Carolina, United States, 27607
United States, South Carolina
GSK Investigational Site
Greenville, South Carolina, United States, 29605
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78731
GSK Investigational Site
Bedford, Texas, United States, 76022
GSK Investigational Site
Dallas, Texas, United States, 75246
GSK Investigational Site
El Paso, Texas, United States, 79915
GSK Investigational Site
Fort Worth, Texas, United States, 76104
GSK Investigational Site
Tyler, Texas, United States, 75702
GSK Investigational Site
Webster, Texas, United States, 77598-4420
United States, Virginia
GSK Investigational Site
Leesburg, Virginia, United States, 20176
GSK Investigational Site
Newport News, Virginia, United States, 23606
United States, Washington
GSK Investigational Site
Spokane, Washington, United States, 99202
GSK Investigational Site
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00447226     History of Changes
Other Study ID Numbers: LPT108741
Study First Received: March 13, 2007
Results First Received: January 11, 2010
Last Updated: June 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Ovarian Cancer
Bladder Cancer
ErbB2 positive
Lapatinib
Gastric/Esophageal Cancer
Uterine Serous Papillary Cancer

Additional relevant MeSH terms:
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014