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

Queen Mary University of London

Status and phase

Unknown

Phase 3

Phase 2

Conditions

Bladder Cancer

Treatments

Other: Placebo

Drug: lapatinib ditosylate

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00949455

EUDRACT-2007-001826-28

EU-20929

BL-2007-02

CDR0000640393

OCTG-LaMB

Details and patient eligibility

About

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.

Full 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.

Enrollment

204 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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:
- 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