A Phase 0 of Neoadjuvant Lapatinib in Infiltrative Bladder Carcinoma Before Cystectomy (LAPAINBLAD)
Modification of the EGF signalling pathway and / or HER 2, by Lapatinib in bladder cancer.
Infiltrative Bladder Carcinoma
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Pilot Study of Lapatinib (Tyverb®) in Neoadjuvant Treatment for Patients With Locally Bladder Carcinoma Before Cystectomy|
- Effect on egf pathway at a molecular level of 3 weeks treatment by lapatinib. [ Time Frame: At surgery (day 21-27) ] [ Designated as safety issue: Yes ]The primary objective of the study is to evaluate the effect at a molecular level, of 3 weeks of neoadjuvant lapatinib, in locally advanced muscle-invasive transitional cell carcinoma of the bladder. A comparison of tissue from the original biopsy and cystectomy after lapatinib will allow this to occur. This effect will be evaluated by studying proliferation and apoptotic markers as well as the phosphorylation of proteins which are components of the egf signalling pathway.
- 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) ] [ Designated as safety issue: Yes ]Because the availability of large scale data, the correlation between lapatinib biological response and the molecular alteration of other molecules beside those involved in the egf pathway will be explored. i.e. key molecules of the pathway will also be studied at the protein level (EGFR, ERBB2, AKT ERK) as well as their phosphorylation status.
- Histological response [ Time Frame: At surgery (day 21-27) ] [ Designated as safety issue: Yes ]To evaluate the histological response to lapatinib at the time of surgery
|Study Start Date:||January 2011|
|Study Completion Date:||October 2011|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Lapatinib, 1250 mg per day, per os, during 3 weeks +/- 5 days.
Patients with invasive bladder tumor , candidates for radical cystectomy. Patients will receive Lapatinib during 3 weeks +/- 5 days, before cystectomy. A comparison of tissue from the original biopsy and cystectomy after Lapatinib will allow this to occur.
TREATMENT AND STRATEGY Lapatinib in bladder carcinoma -Overall there are arguments for considering that egf pathway is involved in bladder carcinoma and so far that drugs inhibiting EGF pathway could have an impact for therapeutical endpoints.
Nevertheless it is unclear that from previous studies that adding egf inhibiting drug to chemotherapy is clinically relevant, essentially by difficulties to measure a beneficial endpoint while downstream EGF pathways have been modified by these drugs, as shown with lapatinib (see 2.1.5).
Furthermore, there is no argument for initial selection of patients based on the initial egfr and/or her 2 tumor profile, asking for more intense knowledge.
LAPATINIB TREATMENT Patients will receive lapatinib therapy at a daily standard dose of 1500 mg.
LAPATINIB TREATMENT DURATION Patients will then receive 3 weeks of lapatinib therapy + possible 5 days. As the study is a non direct benefit study, the exposition to the drug is proposed during the standard window of 3 to 4 weeks to organize a radical cystectomy in patients with muscle invasive bladder carcinoma. In this study patients, the standard procedure is not delayed for the purpose of the study.
The duration of exposition to lapatinib as to be long enough to have a continuous impact of biological events to induce indeed inhibition of EGF pathway but also to impact on more complex or more distal events as apoptosis and so to be able to measure it. This justifies a 3 weeks of treatment + possible up to 5 days more due to surgical organization procedures.
Surgery will take place on the last day of treatment, which is recommended due to the half-life of lapatinib. Nevertheless for surgical purpose, the drug could be not given on the day of surgery.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01245660
|CHU Bordeaux - Hôpital Saint André - Department of Medical Oncology|
|Bordeaux, France, 33075|
|Study Chair:||Geneviève CHENE, Pr||USMR Bordeaux|