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LaMB: A Double Blind Randomised Study of Lapatinib and Placebo in Metastatic TCC of the Urothelium

Sponsor
Queen Mary University of London (Other)
Overall Status
Unknown status
CT.gov ID
NCT00949455
Collaborator
GlaxoSmithKline (Industry)
204
Enrollment
27
Locations
2
Arms
7.6
Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether lapatinib ditosylate is more effective than a placebo in killing tumor cells.

PURPOSE: This randomized phase II/III trial is studying how well lapatinib ditosylate works compared to a placebo in treating patients with stage IV bladder cancer.

Condition or Disease Intervention/Treatment Phase
  • Drug: lapatinib ditosylate
  • Other: Placebo
 Phase 2/Phase 3

Detailed Description

OBJECTIVES:

Primary

  • Compare progression-free survival in patients with HER1- and/or HER2-overexpressing stage IV bladder cancer who have been randomized to maintenance therapy with lapatinib ditosylate or placebo following first-line chemotherapy.

Secondary

  • Compare overall survival between these patient groups.

  • Evaluate the safety and tolerability of the regimens in these patients.

  • Assess and compare quality of life between these patient groups.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status and response to first line chemotherapy (complete or partial response vs stable disease). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity.

  • Arm II: Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity.

Patients undergo quality of life assessment by EORTC QLQ-C30 at baseline and every 4 weeks during study treatment.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
204 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase II/III, Randomised, Two-Arm, Comparison of Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With HER1 and/or HER2 Overexpressing Locally Advanced or Metastatic Bladder Cancer [LaMB]
Study Start Date :
Mar 1, 2009
Anticipated Primary Completion Date :
Jul 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I

Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity.

Drug: lapatinib ditosylate
Given orally
Other Names:
  • Tykerb
  • Tyverb

    		•
    Placebo Comparator: Arm II

    Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity.

    Other: Placebo
    Given orally

    Outcome Measures

    Primary Outcome Measures

    1. Progression free survival [Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.]

    Secondary Outcome Measures

    1. Overall survival []

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    DISEASE CHARACTERISTICS:

    • Histologically confirmed transitional cell carcinoma of the bladder

    • Stage IV disease

    • Metastatic or locally advanced disease

    • HER1- and/or HER2-positive disease, defined by the following criteria:

    • 2+ or 3+ intensity on IHC

    • Able to commence the study treatment within 10 weeks of completing chemotherapy

    • Must have achieved objective response or stable disease following 4-8 courses of first-line chemotherapy

    • No progression with first-line chemotherapy for metastatic disease

    • Any widely accepted chemotherapy regimen for bladder cancer allowed

    • Patients who did not receive cisplatin are eligible

    PATIENT CHARACTERISTICS:

    • ECOG performance status 0-3

    • ANC ≥ 1.0 x 10^9/L

    • Hemoglobin ≥ 8.0 g/dL

    • Platelet count ≥ 75 x 10^9/L

    • ALT/AST < 2 times upper limit of normal (ULN)

    • Bilirubin < 1.5 times ULN

    • Serum creatinine ≤ 3.0 ULN AND/OR creatinine clearance ≥ 30 mL/min

    • LVEF ≥ 50% (as assessed by quantitative echocardiogram or MUGA)

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • No current active hepatic or biliary disease, except for any of the following:

    • Gilbert's syndrome

    • Asymptomatic gallstones

    • Liver metastases

    • Stable chronic liver disease per investigator assessment

    • No known hypersensitivity to the study medication

    • No history of prior or concurrent other neoplasms, except for:

    • Any non life-threatening tumours that have been curatively treated.

    • Prostate cancer isolated to the prostate gland

    • No significant cardiac disease, including any of the following:

    • Angina pectoris

    • Severe cardiac arrhythmia requiring medication

    • Severe conduction abnormalities

    • Clinically significant valvular disease

    • Cardiomegaly

    • Prior myocardial infarction

    • Ventricular hypertrophy

    • Congestive heart failure

    • Poorly uncontrolled hypertension (resting diastolic blood pressure > 115 mm Hg)

    • Other cardiomyopathy

    • No serious intercurrent medical or psychiatric illness

    • No serious active infection

    PRIOR CONCURRENT THERAPY:

    • See Disease Characteristics

    • No more than 1 line of prior chemotherapy for metastatic or locally advanced disease (neoadjuvant/adjuvant chemotherapy allowed)

    • No more than 10 weeks since first-line chemotherapy

    • No prior lapatinib ditosylate

    • No prior radiotherapy to the indicator lesion(s) (newly arising lesions in previously irradiated areas allowed)

    • At least 14 days since prior and no concurrent CYP3A4 inducers, including but not limited to, any of the following:

    • Antibiotics (all rifamycin class agents [e.g., rifampicin, rifabutin, rifapentine])

    • Anticonvulsants (phenytoin, carbamazepine, barbiturates [e.g., phenobarbital])

    • Oral glucocorticoids (cortisone [> 50 mg], hydrocortisone [> 40 mg], prednisone [> 10 mg], methylprednisolone [> 8 mg], dexamethasone [> 2 mg²])

    • St. John's wort or modafinil

    • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including but not limited to, any of the following:

    • Antibiotics (clarithromycin, erythromycin, troleandomycin)

    • Antifungals (itraconazole, ketoconazole, fluconazole [>150 mg daily], voriconazole)

    • Antiretrovirals/protease inhibitors (delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir)

    • Calcium channel blockers (verapamil, diltiazem)

    • Antidepressants (nefazodone, fluvoxamine)

    • Gastrointestinal agents (cimetidine, aprepitant)

    • Grapefruit, grapefruit juice

    • At least 6 months since prior and no concurrent amiodarone

    • No concurrent radical or curative therapy (radiotherapy or surgery) at the end of first-line treatment (palliative radiotherapy allowed)

    • No other concurrent experimental or investigational drugs

    • No other concurrent anticancer treatment, including cytotoxic or specific immune therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Barts and the London NHS Trust London England United Kingdom EC1M 6BQ
    2 NHS Grampian - Aberdeen Royal Infirmary Aberdeen United Kingdom
    3 Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital Basildon United Kingdom
    4 University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital Birmingham United Kingdom
    5 Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital Bournemouth United Kingdom
    6 University Hospitals Bristol NHS Trust - Bristol University Hospital Bristol United Kingdom
    7 Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital Cambridge United Kingdom
    8 Mid Essex NHS Trust - Broomfield Hospital Chelmsford United Kingdom
    9 Colchester University Hospitals NHS Trust Colchester United Kingdom
    10 University Hospitals Coventry & Warwickshire NHS Trust Coventry United Kingdom
    11 Derby Hospitals NHS Trust - Royal Derby Hospital Derby United Kingdom
    12 NHS Greater Glasgow and Clyde - The Beatson Glasgow United Kingdom
    13 Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary Huddersfield United Kingdom
    14 Ipswich Hospital NHS Trust Ipswich United Kingdom
    15 University Hospitals of Leicester NHS Trust Leicester United Kingdom
    16 Clatterbridge Centre for Oncology NHS Trust Liverpool United Kingdom
    17 Guys & St Thomas' Hospital NHS Trust - Guys Hospital London United Kingdom
    18 Imperial Healthcare NHS Trust London United Kingdom
    19 Royal Marsden NHS Trust London United Kingdom
    20 South Tees NHS Trust - James Cook University Hospital Middlesborough United Kingdom
    21 Newcastle Upon Tyne Hospitals NHS Trust Newcastle United Kingdom
    22 Northampton General Hospitals NHS Trust Northampton United Kingdom
    23 Nottingham University Hospitals NHS Trust Nottingham United Kingdom
    24 Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital Nottingham United Kingdom
    25 Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital Portsmouth United Kingdom
    26 Barking, Havering and Redbridge NHS Trust - Queens Hospital Romford United Kingdom
    27 Taunton and Somerset NHS Trust - Musgrove Park Hospital Taunton United Kingdom

    Sponsors and Collaborators

    • Queen Mary University of London
    • GlaxoSmithKline

    Investigators

    • Principal Investigator: Thomas Powles, MD, MRCP, Queen Mary University of London

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00949455
    Other Study ID Numbers:
    • CDR0000640393
    • OCTG-LaMB
    • BL-2007-02
    • EUDRACT-2007-001826-28
    • EU-20929
    First Posted:
    Jul 30, 2009
    Last Update Posted:
    Apr 15, 2015
    Last Verified:
    Apr 1, 2015
    Keywords provided by , ,
    stage IV bladder cancer
    transitional cell carcinoma of the bladder
    Additional relevant MeSH terms:
    Urinary Bladder Neoplasms
    Lapatinib

    Study Results

    No Results Posted as of Apr 15, 2015