- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00949455
A Double Blind Randomised Study of Lapatinib and Placebo in Metastatic TCC of the Urothelium (LaMB)
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]
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
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Aberdeen, United Kingdom
- NHS Grampian - Aberdeen Royal Infirmary
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Basildon, United Kingdom
- Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital
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Birmingham, United Kingdom
- University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital
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Bournemouth, United Kingdom
- Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital
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Bristol, United Kingdom
- University Hospitals Bristol NHS Trust - Bristol University Hospital
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Cambridge, United Kingdom
- Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital
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Chelmsford, United Kingdom
- Mid Essex NHS Trust - Broomfield Hospital
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Colchester, United Kingdom
- Colchester University Hospitals NHS Trust
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Coventry, United Kingdom
- University Hospitals Coventry & Warwickshire NHS Trust
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Derby, United Kingdom
- Derby Hospitals NHS Trust - Royal Derby Hospital
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Glasgow, United Kingdom
- NHS Greater Glasgow and Clyde - The Beatson
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Huddersfield, United Kingdom
- Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary
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Ipswich, United Kingdom
- Ipswich Hospital NHS Trust
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Leicester, United Kingdom
- University Hospitals Of Leicester Nhs Trust
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Liverpool, United Kingdom
- Clatterbridge Centre for Oncology NHS Trust
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London, United Kingdom
- Imperial Healthcare NHS Trust
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London, United Kingdom
- Guys & St Thomas' Hospital NHS Trust - Guys Hospital
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London, United Kingdom
- Royal Marsden NHS Trust
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Middlesborough, United Kingdom
- South Tees NHS Trust - James Cook University Hospital
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Newcastle, United Kingdom
- Newcastle Upon Tyne Hospitals NHS Trust
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Northampton, United Kingdom
- Northampton General Hospitals NHS Trust
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Nottingham, United Kingdom
- Nottingham University Hospitals NHS Trust
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Nottingham, United Kingdom
- Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital
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Portsmouth, United Kingdom
- Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
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Romford, United Kingdom
- Barking, Havering and Redbridge NHS Trust - Queens Hospital
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Taunton, United Kingdom
- Taunton and Somerset NHS Trust - Musgrove Park Hospital
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England
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London, England, United Kingdom, EC1M 6BQ
- Barts and the London NHS Trust
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I
Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity.
|
Given orally
Other Names:
|
Placebo Comparator: Arm II
Patients receive oral placebo once daily in the absence of disease progression or unacceptable toxicity.
|
Given orally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression free survival
Time Frame: Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.
|
Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.
|
Secondary Outcome Measures
Outcome Measure |
---|
Overall survival
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Thomas Powles, MD, MRCP, Queen Mary University of London
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CDR0000640393
- OCTG-LaMB
- BL-2007-02
- EUDRACT-2007-001826-28
- EU-20929
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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