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

Bladder Cancer Clinical Trial

— LaMB  

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]

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00949455
• Other study ID #: CDR0000640393
• Secondary ID: OCTG-LaMBBL-2007
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: July 29, 2009
• Last updated: April 14, 2015
• Start date: March 2009

Study information

• Verified date: April 2015
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 204
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• lapatinib ditosylate
Given orally

Other:
• Placebo
Given orally

Locations

Country	Name	City	State
United Kingdom	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	Barts and the London NHS Trust	London	England
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

Sponsors (2)

Lead Sponsor	Collaborator
Queen Mary University of London	GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.	No
Secondary	Overall survival			No