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

NCT ID: NCT00949455

Last Updated: 2015-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

204 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Bladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm I

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

Group Type EXPERIMENTAL

lapatinib ditosylate

Intervention Type DRUG

Given orally

Arm II

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Given orally

Interventions

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lapatinib ditosylate

Given orally

Intervention Type DRUG

Placebo

Given orally

Intervention Type OTHER

Other Intervention Names

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Tykerb Tyverb

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Queen Mary University of London

OTHER

Sponsor Role lead

Principal Investigators

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Thomas Powles, MD, MRCP

Role: PRINCIPAL_INVESTIGATOR

Queen Mary University of London

Locations

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Barts and the London NHS Trust

London, England, United Kingdom

Site Status

NHS Grampian - Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital

Basildon, , United Kingdom

Site Status

University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital

Birmingham, , United Kingdom

Site Status

Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital

Bournemouth, , United Kingdom

Site Status

University Hospitals Bristol NHS Trust - Bristol University Hospital

Bristol, , United Kingdom

Site Status

Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Mid Essex NHS Trust - Broomfield Hospital

Chelmsford, , United Kingdom

Site Status

Colchester University Hospitals NHS Trust

Colchester, , United Kingdom

Site Status

University Hospitals Coventry & Warwickshire NHS Trust

Coventry, , United Kingdom

Site Status

Derby Hospitals NHS Trust - Royal Derby Hospital

Derby, , United Kingdom

Site Status

NHS Greater Glasgow and Clyde - The Beatson

Glasgow, , United Kingdom

Site Status

Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary

Huddersfield, , United Kingdom

Site Status

Ipswich Hospital NHS Trust

Ipswich, , United Kingdom

Site Status

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

Site Status

Clatterbridge Centre for Oncology NHS Trust

Liverpool, , United Kingdom

Site Status

Guys & St Thomas' Hospital NHS Trust - Guys Hospital

London, , United Kingdom

Site Status

Imperial Healthcare NHS Trust

London, , United Kingdom

Site Status

Royal Marsden NHS Trust

London, , United Kingdom

Site Status

South Tees NHS Trust - James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status

Newcastle Upon Tyne Hospitals NHS Trust

Newcastle, , United Kingdom

Site Status

Northampton General Hospitals NHS Trust

Northampton, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital

Nottingham, , United Kingdom

Site Status

Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital

Portsmouth, , United Kingdom

Site Status

Barking, Havering and Redbridge NHS Trust - Queens Hospital

Romford, , United Kingdom

Site Status

Taunton and Somerset NHS Trust - Musgrove Park Hospital

Taunton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Bellmunt J, Werner L, Bamias A, Fay AP, Park RS, Riester M, Selvarajah S, Barletta JA, Berman DM, de Muga S, Salido M, Gallardo E, Rojo F, Guancial EA, Bambury R, Mullane SA, Choueiri TK, Loda M, Stack E, Rosenberg J. HER2 as a target in invasive urothelial carcinoma. Cancer Med. 2015 Jun;4(6):844-52. doi: 10.1002/cam4.432. Epub 2015 Feb 26.

Reference Type DERIVED
PMID: 25720673 (View on PubMed)

Other Identifiers

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OCTG-LaMB

Identifier Type: -

Identifier Source: secondary_id

BL-2007-02

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-001826-28

Identifier Type: -

Identifier Source: secondary_id

EU-20929

Identifier Type: -

Identifier Source: secondary_id

CDR0000640393

Identifier Type: -

Identifier Source: org_study_id

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