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

NCT00949455 | Unknown Phase 2 DMC

• 5 other identifiers: CDR0000640393OCTG-LaMBBL-2007-02EUDRACT-2007-001826-28EU-20929
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 27

Brief 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.

Conditions

Bladder Cancer

Keywords

stage IV bladder cancer; transitional cell carcinoma of the bladder

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Disease Progression - at least 20% increase in the sum of longest diameters of target lesions.

Secondary Outcomes (1)

• Overall survival

Study Arms (2)

Arm I

EXPERIMENTAL

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

Drug: lapatinib ditosylate

Arm II

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

lapatinib ditosylate DRUG

Given orally

Also known as: Tykerb, Tyverb

Arm I

Placebo OTHER

Given orally

Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Queen Mary University of London: lead
• GlaxoSmithKline: collaborator

Study Sites (27)

Barts and the London NHS Trust

London, England, EC1M 6BQ, United Kingdom

Location

NHS Grampian - Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Basildon and Thurrock University Hospital NHS Trust - Basildon Hospital

Basildon, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust - Birmingham University Hospital

Birmingham, United Kingdom

Location

Royal Bournemouth and Christchurch NHS Foundation Trust - Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

University Hospitals Bristol NHS Trust - Bristol University Hospital

Bristol, United Kingdom

Location

Cambridge University Hospitals NHS Trust - Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Mid Essex NHS Trust - Broomfield Hospital

Chelmsford, United Kingdom

Location

Colchester University Hospitals NHS Trust

Colchester, United Kingdom

Location

University Hospitals Coventry & Warwickshire NHS Trust

Coventry, United Kingdom

Location

Derby Hospitals NHS Trust - Royal Derby Hospital

Derby, United Kingdom

Location

NHS Greater Glasgow and Clyde - The Beatson

Glasgow, United Kingdom

Location

Calderdale and Huddersfield NHS Trust - Huddersfield Royal Infirmary

Huddersfield, United Kingdom

Location

Ipswich Hospital NHS Trust

Ipswich, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

Location

Clatterbridge Centre for Oncology NHS Trust

Liverpool, United Kingdom

Location

Guys & St Thomas' Hospital NHS Trust - Guys Hospital

London, United Kingdom

Location

Imperial Healthcare NHS Trust

London, United Kingdom

Location

Royal Marsden NHS Trust

London, United Kingdom

Location

South Tees NHS Trust - James Cook University Hospital

Middlesbrough, United Kingdom

Location

Newcastle Upon Tyne Hospitals NHS Trust

Newcastle, United Kingdom

Location

Northampton General Hospitals NHS Trust

Northampton, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Sherwood Forest Hospitals NHS Trust - Kings Mill Hospital

Nottingham, United Kingdom

Location

Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital

Portsmouth, United Kingdom

Location

Barking, Havering and Redbridge NHS Trust - Queens Hospital

Romford, United Kingdom

Location

Taunton and Somerset NHS Trust - Musgrove Park Hospital

Taunton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25720673 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Thomas Powles, MD, MRCP

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: July 30, 2009
• Study Start: March 1, 2009
• Primary Completion: July 1, 2015
• Last Updated: April 15, 2015

Record last verified: 2015-04

Locations

GB (27)