Pilot study of Lapatinib (Tyverb®) in néoadjuvant treatment for patients with locally bladder carcinoma before cystectomy - LAPAINBLAD

• Conditions: Bladder carcinoma; MedDRA version: 9.1Level: LLTClassification code 10005015Term: Bladder carcinoma NOS

• Registration Number: EUCTR2009-012714-49-FR
• Lead Sponsor: CHU de Bordeaux

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
-> Patients must sign and date IRB/EC-approved informed consent.
-> Age = 18.

-> A female is eligible to enter and participate in this study if she is of:
- Non-child-bearing potential (i.e., a woman with functioning ovaries who have a current documented tubal ligation or hysterectomy or a woman who is menopausal), or
- child-bearing potential (i.e. a woman with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (even severe), women who are perimenopausal and young women who have begun to menstruate), who have a negative serum pregnancy test at screening, and agree to one of the following,
or
- Consistent and correct use of one of the following acceptable methods of birth control, or
- Any intrauterine device (IUD) with a documented failure rate of less than 1% per yearn or
- Combined oral contraception,

-> Care must be taken to avoid pregnancy in partners of male patients,
-> Patients must have a life expectancy of at least 6 months,
-> Patients must have a Karnofsky performance status = 80%,
-> Clinical stage T2NxM0 to T4aNxM0 bladder cancer,
-> Muscle-invasive transitional cell carcinoma by histology (focal squamous and/or adenocarcinoma differentiation defined as = 10% of tumor volume allowed, sarcomatoid and small-cell components not allowed),
-> Considered to have a macroscopic residue in the bladder to allow comparison of tissue samples at cystectomy to initial biopsies,
-> Candidates for radical cystectomy,
-> Patient with normal cardiac function, LVEF = 50% measured by echocardiography or MUGA scan,
-> Able to swallow and retain oral medication,
-> Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures,
-> Affiliated or profit patient of a social security system

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-> Prior pelvic radiation or neoadjuvant chemotherapy.
-> Pregnancy or breastfeeding.
-> Other severe acute or chronic medical or psychiatric condition that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
-> Patients with significantly reduced LVEF or LVEF < 50%.
-> Patient with any of the following liver abnormal laboratory test :
- Serum bilirubin > 1,5 x upper limit of normal (ULN) (in case of Gilbert syndrome, a higher serum total bilirubin (< 2 ULN) is allowed
- Alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2,5 ULN
- Platelets ? 100 x 109/L, hemoglobin > 9 g/dl, absolute neutrophil count (ANC) >1.5 x 109/L
-> Serum creatinine < 1.5 x ULN.
-> Previous therapy targeting EGFR or HER-2.
-> Predominantly non transitional cell histology.
-> Pregnant or lactating females. NOTE: A negative pregnancy test must be documented during the screening period for women of childbearing potential
-> Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months.
-> Malabsorption syndrome, disease significantly affecting gastrointestinal function, or major resection of the stomach or bowel, that could affect absorption of lapatinib.
-> History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
-> Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, that would limit compliance with study requirements.
- History of uncontrolled or symptomatic angina
- History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
- Myocardial infarction < 6 months from study entry
- Uncontrolled or symptomatic congestive heart failure
- Ejection fraction below the institutional normal limit
- Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
-> Use of an investigational agent within 30 days or 5 half-lives, whichever is the longer, preceding the first dose of investigational product.
-> Concurrent treatment with an investigational agent
-> Concurrent treatment with cytotoxic chemotherapy, immunotherapy, biologic therapy, hormonal therapy or curative radiotherapy for locally advanced or metastatic TCC of the urothelial tract.
-> Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
-> 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)
-> Patient under safeguard of justice

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified