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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Queen Mary University of London
ClinicalTrials.gov Identifier:
NCT00949455
First received: July 29, 2009
Last updated: July 11, 2014
Last verified: July 2014
  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: December 2014 (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
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: NCT00949455

Locations
United Kingdom
Barts and the London NHS Trust
London, England, United Kingdom, EC1M 6BQ
NHS Grampian - Aberdeen Royal Infirmary
Aberdeen, United Kingdom
Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital
Basildon, United Kingdom
University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital
Birmingham, United Kingdom
Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital
Bournemouth, United Kingdom
University Hospitals Bristol NHS Trust - Bristol University Hospital
Bristol, United Kingdom
Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital
Cambridge, United Kingdom
Mid Essex NHS Trust - Broomfield Hospital
Chelmsford, United Kingdom
Colchester University Hospitals NHS Trust
Colchester, United Kingdom
University Hospitals Coventry & Warwickshire NHS Trust
Coventry, United Kingdom
Derby Hospitals NHS Trust - Royal Derby Hospital
Derby, United Kingdom
NHS Greater Glasgow and Clyde - The Beatson
Glasgow, United Kingdom
Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary
Huddersfield, United Kingdom
Ipswich Hospital NHS Trust
Ipswich, United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, United Kingdom
Clatterbridge Centre for Oncology NHS Trust
Liverpool, United Kingdom
Guys & St Thomas' Hospital NHS Trust - Guys Hospital
London, United Kingdom
Imperial Healthcare NHS Trust
London, United Kingdom
Royal Marsden NHS Trust
London, United Kingdom
South Tees NHS Trust - James Cook University Hospital
Middlesborough, United Kingdom
Newcastle Upon Tyne Hospitals NHS Trust
Newcastle, United Kingdom
Northampton General Hospitals NHS Trust
Northampton, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital
Nottingham, United Kingdom
Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
Portsmouth, United Kingdom
Barking, Havering and Redbridge NHS Trust - Queens Hospital
Romford, United Kingdom
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
  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: July 11, 2014
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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014