A Phase 0 of Neoadjuvant Lapatinib in Infiltrative Bladder Carcinoma Before Cystectomy

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01245660
• Date of registration: 18/11/2010
• Prospective Registration: Yes
• Primary sponsor: University Hospital, Bordeaux
• Public title: A Phase 0 of Neoadjuvant Lapatinib in Infiltrative Bladder Carcinoma Before Cystectomy LAPAINBLAD
• Scientific title: Pilot Study of Lapatinib (Tyverb®) in Neoadjuvant Treatment for Patients With Locally Bladder Carcinoma Before Cystectomy
• Date of first enrolment: January 2011
• Target sample size: 3
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01245660
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
• Phase: Phase 0

Countries of recruitment

France, United Kingdom

Contacts

• Name: Geneviève CHENE, Pr
• Affiliation: USMR Bordeaux

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients must sign and date IRB/EC-approved informed consent,

- Age = 18

- 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

- 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 consistent and
correct use of one acceptable methods of birth control : Any intrauterine device
(IUD) with a documented failure rate of less than 1% per year, or combined oral
contraception

- care must be taken to avoid pregnancy in partners of male patients.

- 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

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

- 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)

- Serum creatinine > 1.5 x ULN.

- Previous therapy targeting EGFR or HER-2.

- Predominantly non transitional cell histology.

- 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.

- Patient under safeguard of justice



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Infiltrative Bladder Carcinoma

Bladder Carcinoma

Cystectomy

Intervention(s)

Drug: LAPATINIB

Primary Outcome(s)

Effect on egf pathway at a molecular level of 3 weeks treatment by lapatinib. [Time Frame: At surgery (day 21-27)]

Secondary Outcome(s)

Lapatinib biological response on key molecules of the egf pathway (EGFR, ERBB2, AKT ERK as well as their phosphorylation status.) [Time Frame: At screening (day -10 before inclusion) , surgery (day 21-27) and Follow up visit surgery (day 42-62)]

Histological response [Time Frame: At surgery (day 21-27)]

Secondary ID(s)

CHUBX 2009/04

Source(s) of Monetary Support

Please refer to primary and secondary sponsors