E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The medical condition being investigated in this trial is locally advanced or metastatic urological cancer. The tumour must overexpress HER1 and/or HER2 gene. |
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E.1.1.1 | Medical condition in easily understood language |
Bladder cancer that has spread to other parts of the body or to nearby tissues in the area. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005012 |
E.1.2 | Term | Bladder cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 2 x ULN, bilirubin level < 1.5 x ULN). •Normal cardiac function with a left ventricular ejection fraction of at least 50% (as assessed by quantitative echocardiogram) •ECOG performance status 0-3 •Age ≥ 18 years •If the patient is of childbearing potential, she agrees to: comply with effective contraceptive measures, has been using adequate contraception since the last menses, will use adequate contraception during the study, and has a negative pregnancy test within one week of study entry •Written informed consent prior to admission to this study |
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E.4 | Principal 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 <30 ml/min (using EDTA or Cockcroft and Gault) •Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) •Previous treatment with study medication and/or known hypersensitivity to the study medication. •Past or current history of other neoplasms, except for: o Any non life-threatening tumours that have been curatively treated. •Significant cardiac disease, including angina pectoris, severe cardiac arrhythmia requiring medication, severe conduction abnormalities, clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, poorly uncontrolled hypertension (resting diastolic blood pressure >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
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This will occur after 196 events have been reached. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 35 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial is defined as thirty days after the last patient has taken the last study dose to allow for all safety reporting. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |