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CancerPhase 2NCT00447226

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

A Phase 2 study of Cancer, run by GlaxoSmithKline at 20 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
20 sitesUnited States
Study dates
May 2007to Sep 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • GSK Investigational Site

    Albany, New York, 12206

  • GSK Investigational Site

    Austin, Texas, 78731

  • GSK Investigational Site

    Bedford, Texas, 76022

  • GSK Investigational Site

    Dallas, Texas, 75246

  • GSK Investigational Site

    Denver, Colorado, 80218

  • GSK Investigational Site

    El Paso, Texas, 79915

  • GSK Investigational Site

    Fort Worth, Texas, 76104

  • GSK Investigational Site

    Greenville, South Carolina, 29605

  • GSK Investigational Site

    Indianapolis, Indiana, 46219

  • GSK Investigational Site

    Las Vegas, Nevada, 89109

  • GSK Investigational Site

    Leesburg, Virginia, 20176

  • GSK Investigational Site

    Minneapolis, Minnesota, 55404

  • GSK Investigational Site

    Newport News, Virginia, 23606

  • GSK Investigational Site

    Overland Park, Kansas, 66210

  • GSK Investigational Site

    Raleigh, North Carolina, 27607

  • GSK Investigational Site

    Spokane, Washington, 99202

  • GSK Investigational Site

    St Louis, Missouri, 63141

  • GSK Investigational Site

    Tyler, Texas, 75702

  • GSK Investigational Site

    Vancouver, Washington, 98684

  • GSK Investigational Site

    Webster, Texas, 77598-4420

Other trials in United States

About this study

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

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
Being tested
Oral lapatinib tablets or placebo tablets
Keywords
Ovarian Cancer, Bladder Cancer, ErbB2 positive, Lapatinib, Gastric/Esophageal Cancer, Uterine Serous Papillary Cancer
Medical subject headings
Neoplasms, Ovarian Neoplasms, Urinary Bladder Neoplasms, Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral lapatinib tablets or placebo tabletsDrug

    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.

Study groups in NCT00447226
Study groupRoleWhat they receive
Lapatinib Oral TabletsExperimentalNot described
Receives: Drug: Oral lapatinib tablets or placebo tablets
Placebo ControlPlacebo comparatorNot described
Receives: Drug: Oral lapatinib tablets or placebo tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Week 12

  2. 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.

    Measured: Week 12 after randomization.

Secondary outcomes (6)

  1. Duration of Response

    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.

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

  2. Progression-free Survival (PFS)

    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.

    Measured: 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)

  3. Time to Disease Progression (TTP)

    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.

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

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

    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.

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

  5. Incidence of MET Amplification in Gastric Cancer

    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.

    Measured: Performed on archived tissue collected at screening.

  6. Incidence of ErbB2-positive Participants

    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.

    Measured: Screening

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionMay 2009
  4. Study completionSep 2009

Why it stopped: The study had failed to meet the primary objective of tumor response rate at 12 weeks from first dose.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00447226
Sponsor's protocol ID
LPT108741
Status last verified
Jun 2012
First submitted
13 Mar 2007
Last updated
12 Jun 2012
Data monitoring committee
No

Publications

  • 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.

    PubMed 20857170

Questions about this trial

What is this clinical trial studying?

A Phase 2 study of Cancer, run by GlaxoSmithKline at 20 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Feb 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With the Indicated Tumor Response at 12 Weeks From First Dose (time frame: Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00447226, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2012.

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