The medical condition being investigated in this trial is locally advanced or metastatic urological cancer. The tumour must overexpress HER1 and/or HER2 gene. MedDRA version: 17.1 Level: PT Classification code 10005012 Term: Bladder cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tyverb
Product Name: lapatinib
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
CAS Number: 388082-78-8
Sponsors
Queen Mary University London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Histologically confirmed metastatic or locally advanced transitional cell carcinoma of the urothelium. •Stage IV disease at entry of the study •Able to commence study treatment within 10 weeks of completing chemotherapy •HER1-positive (2+ or 3+ intensity on immunohistochemical staining (IHC) and/or amplification of the HER1 gene on fluorescence in situ hybridization (FISH)) and/or HER2-positive (2+ or 3+ intensity on immunohistochemical staining (IHC) and/or amplification of the HER2 gene on FISH) •Objective response or stable disease following at least 4 and no more than 8 cycles of first-line chemotherapy. The chemotherapy regimen includes any widely accepted regimen for bladder cancer. Patients who do not receive cisplatin remain eligible. Dose reduction and delays in treatment between cycles are acceptable. •Adequate haematological function (ANC =1.0 x 109/l, Hb = 8.0 g/dL and platelet count to =75 x 109/l). •Adequate liver function tests (ALT/AST =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: •Patients who progress by RECIST on first-line chemotherapy and require 2nd line chemotherapy. Patients with progression of disease who do not fulfil RECIST criteria for PD and do not require 2nd line therapy are eligible. The original pre-treatment CT and post treatment CT should be compared to assess response. •More than one line of prior chemotherapy for metastatic or locally advanced disease (Neoadjuvant/adjuvant chemotherapy is acceptable). •Serum creatinine concentration > 3.0 x ULN and/or creatinine clearance 115 mmHg), prior myocardial infarction, CHF, or other cardiomyopathy • Serious intercurrent medical or psychiatric illness, including serious active infection • Concurrent treatment with other experimental drugs. • Less than 4 cycles or more than 8 cycles of standard chemotherapy •Greater than 10 week delay from finishing 1st line chemotherapy to starting maintenance therapy. • Pregnant or nursing women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the study is to compare progression-free survival (PFS) in patients with HER1 and/or HER2 over expressing stage IV bladder cancer who have been randomised to maintenance therapy with lapatinib or placebo following first-line chemotherapy; Secondary Objective: The secondary objectives of this study are to: • Compare overall survival (OS) between the two groups. • Evaluate the safety and tolerability of the regimens in this population • Assess and compare quality of life between the 2 groups • Assess best response rate (RR) between the two groups • Investigate the correlation of outcome with baseline characteristics of different HER1-4 intensities of overexpression ;Primary end point(s): The primary end point of the trial is to compare PFS for patients randomised to receive placebo versus those randomised to lapatinib. ;Timepoint(s) of evaluation of this end point: This will occur after 196 events have been reached. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives;Timepoint(s) of evaluation of this end point: This will occur after the last patient has taken the last study dose to allow for all safety reporting to be complete. | — |
Countries
United Kingdom
Contacts
Public ContactCharlotte Rofe
Centre for Experimental Cancer Medicine
Outcome results
None listed