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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Queen Mary University of London.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Queen Mary University of London
ClinicalTrials.gov Identifier:
NCT00949455
First received: July 29, 2009
Last updated: June 8, 2012
Last verified: July 2009
  Purpose

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 Intervention Phase
Bladder Cancer
Drug: lapatinib ditosylate
Other: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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]

Resource links provided by NLM:


Further study details as provided by Queen Mary University of London:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Disease Progression - at least 20% increase in the sum of longest diameters of target lesions. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 204
Study Start Date: March 2009
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00949455

Contacts
Contact: Charlotte Rofe c.rofe@qmul.ac.uk

Locations
United Kingdom
Barts and the London NHS Trust Recruiting
London, England, United Kingdom, EC1M 6BQ
Contact: Charlotte Rofe    44-207-882-8497      
Principal Investigator: Thomas Powles         
NHS Grampian - Aberdeen Royal Infirmary Recruiting
Aberdeen, United Kingdom
Principal Investigator: Graham MacDonald         
Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital Recruiting
Basildon, United Kingdom
Principal Investigator: Naveed Sarwar         
University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital Recruiting
Birmingham, United Kingdom
Principal Investigator: Nick James         
Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital Recruiting
Bournemouth, United Kingdom
Principal Investigator: Sue Brock         
University Hospitals Bristol NHS Trust - Bristol University Hospital Recruiting
Bristol, United Kingdom
Principal Investigator: Serena Hilman         
Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Principal Investigator: Danish Mazhur         
Mid Essex NHS Trust - Broomfield Hospital Recruiting
Chelmsford, United Kingdom
Principal Investigator: Kiran Kancherla         
Colchester University Hospitals NHS Trust Active, not recruiting
Colchester, United Kingdom
University Hospitals Coventry & Warwickshire NHS Trust Recruiting
Coventry, United Kingdom
Principal Investigator: Andrew Stockdale         
Derby Hospitals NHS Trust - Royal Derby Hospital Recruiting
Derby, United Kingdom
Principal Investigator: Prabir Chakraborti         
NHS Greater Glasgow and Clyde - The Beatson Recruiting
Glasgow, United Kingdom
Principal Investigator: Rob Jones         
Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary Recruiting
Huddersfield, United Kingdom
Principal Investigator: Uschi Hofmann         
Ipswich Hospital NHS Trust Recruiting
Ipswich, United Kingdom
Principal Investigator: Ram Venkitaraman         
University Hospitals of Leicester NHS Trust Active, not recruiting
Leicester, United Kingdom
Clatterbridge Centre for Oncology NHS Trust Recruiting
Liverpool, United Kingdom
Principal Investigator: Syed Hussain         
Guys & St Thomas' Hospital NHS Trust - Guys Hospital Recruiting
London, United Kingdom
Principal Investigator: Simon Chowdhury         
Imperial Healthcare NHS Trust Active, not recruiting
London, United Kingdom
Royal Marsden NHS Trust Recruiting
London, United Kingdom
Principal Investigator: Robert Huddart         
South Tees NHS Trust - James Cook University Hospital Recruiting
Middlesborough, United Kingdom
Principal Investigator: Hans Van der Voet         
Newcastle Upon Tyne Hospitals NHS Trust Recruiting
Newcastle, United Kingdom
Principal Investigator: John Frew         
Northampton General Hospitals NHS Trust Not yet recruiting
Northampton, United Kingdom
Principal Investigator: Guy Faust         
Nottingham University Hospitals NHS Trust Recruiting
Nottingham, United Kingdom
Principal Investigator: Santhanam Sundar         
Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital Recruiting
Nottingham, United Kingdom
Principal Investigator: Daniel Saunders         
Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital Recruiting
Portsmouth, United Kingdom
Principal Investigator: Joanna Gale         
Barking, Havering and Redbridge NHS Trust - Queens Hospital Recruiting
Romford, United Kingdom
Principal Investigator: Jonathan Shamash         
Sub-Investigator: Stephanie Gibbs         
Taunton and Somerset NHS Trust - Musgrove Park Hospital Recruiting
Taunton, United Kingdom
Principal Investigator: Mohini Varughese         
Sponsors and Collaborators
Queen Mary University of London
GlaxoSmithKline
Investigators
Principal Investigator: Thomas Powles, MD, MRCP Queen Mary University of London
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00949455     History of Changes
Other Study ID Numbers: CDR0000640393, OCTG-LaMB, BL-2007-02, EUDRACT-2007-001826-28, EU-20929
Study First Received: July 29, 2009
Last Updated: June 8, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Queen Mary University of London:
stage IV bladder cancer
transitional cell carcinoma of the bladder

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Lapatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014