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

NCT00447226 | Terminated Phase 2 Results

• 1 other identifier: LPT108741
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 20

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.

Conditions

Cancer

Keywords

Ovarian Cancer; Bladder Cancer; ErbB2 positive; Lapatinib; Gastric/Esophageal Cancer; Uterine Serous Papillary Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose

  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.

  Week 12

• Percentage of Participants Who Remained Progression-free 12 Weeks After Randomization

  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.

  Week 12 after randomization.

Secondary Outcomes (6)

• Duration of Response

  (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib)

• Progression-free Survival (PFS)

  From start of treatment to disease progression/death (assessments every 12 weeks until death for withdrawn participants and every 3 weeks for participants continuing on lapatinib)

• Time to Disease Progression (TTP)

  From start of treatment to disease progression/death (up to 83.3 weeks)

• Number of Participants With the Indicated Change in Cancer Antigen-125 (CA-125) Levels From Day 1

  Pre-dose and every 6 weeks until withdrawal (up to 84.1 weeks)

• Incidence of MET Amplification in Gastric Cancer

  Performed on archived tissue collected at screening.

Study Arms (2)

Lapatinib Oral Tablets

EXPERIMENTAL

Drug: Oral lapatinib tablets or placebo tablets

Placebo Control

PLACEBO COMPARATOR

Drug: Oral lapatinib tablets or placebo tablets

Interventions

Oral lapatinib tablets or placebo tablets DRUG

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.

Lapatinib Oral Tablets; Placebo Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Denver, Colorado, 80218, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46219, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66210, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89109, United States

Location

GSK Investigational Site

Albany, New York, 12206, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27607, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29605, United States

Location

GSK Investigational Site

Austin, Texas, 78731, United States

Location

GSK Investigational Site

Bedford, Texas, 76022, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

El Paso, Texas, 79915, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Tyler, Texas, 75702, United States

Location

GSK Investigational Site

Webster, Texas, 77598-4420, United States

Location

GSK Investigational Site

Leesburg, Virginia, 20176, United States

Location

GSK Investigational Site

Newport News, Virginia, 23606, United States

Location

GSK Investigational Site

Spokane, Washington, 99202, United States

Location

GSK Investigational Site

Vancouver, Washington, 98684, United States

Location

Related Publications (1)

• 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.

  PMID: 20857170 DERIVED

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Urinary Bladder Neoplasms; Esophageal Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Study terminated prematurely: preliminary assessment (prompted by low screening/enrollment rates) showed primary objective of tumor response rate not met. Also unable to test primary treatment comparison after randomization following SD at 12 wks.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2007
• First Posted: March 14, 2007
• Study Start: May 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: September 1, 2009
• Last Updated: June 12, 2012
• Results First Posted: February 4, 2010

Record last verified: 2012-06

Locations

US (20)