Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Lapatinib Ditosylate in Treating Patients With Stage IV Bladder Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Active	18 and over	Other	OCTG-LaMB OCTG-LaMB, BL-2007-02, EUDRACT-2007-001826-28, EU-20929, NCT00949455

Objectives

Primary

1. 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

1. Compare overall survival between these patient groups.
2. Evaluate the safety and tolerability of the regimens in these patients.
3. Assess and compare quality of life between these patient groups.

Entry 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:
  • Gene amplification on FISH
  • 2+ or 3+ intensity on IHC
• Able to commence the study treatment within 8 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

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 8 weeks since first-line chemotherapy
• No prior anti-HER1 or anti-HER2 therapy
• 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

Patient Characteristics:

• ECOG performance status 0-3
• ANC ≥ 1.0 x 10⁹/L
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 75 x 10⁹/L
• ALT/AST < 2 times upper limit of normal (ULN)
• Alkaline phosphatase < 2 times 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 of the following:
  • Curatively treated nonmelanoma skin cancer
  • Adequately treated in situ carcinoma of the cervix
  • Other cancer curatively treated with no evidence of disease for ≥ 5 years
  • 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

Expected Enrollment

Outcomes

Progression-free survival

Overall survival

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.

Trial Contact Information

Trial Lead Organizations

Orchid Clinical Trials Group at Barts and the London School of Medicine and Dentistry

Thomas Powles, MD, MRCP, Principal investigator		Ph: 44-207-882-8761

United Kingdom
England
	London
	Orchid Clinical Trials Group at Barts and the London School of Medicine and Dentistry
		Thomas Powles, MD, MRCP	Ph:  44-207-882-8761

Registry Information
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]
Trial Start Date		2007-11-28
Trial Completion Date		2011-06-01 (estimated)
Registered in ClinicalTrials.gov		NCT00949455
Date Submitted to PDQ		2009-04-08
Information Last Verified		2009-07-28

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