Clinical trial NCT01828736: Efficacy of Combination of Trastuzumab to Gemcitabine - Platinum Advanced or Metastatic Urothelial Carcinoma
Official title: Multicenter Randomized Phase 2 Trial of Gemcitabine - Platinum With or Without Trastuzumab in Advanced or Metastatic Urothelial Carcinoma With HER2 Overexpression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Bladder Cancer
Stage IV Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Keywords: Urothelial carcinoma
Trastuzumab
Treatment
Lead sponsor: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2013-04-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multicenter, randomized, Phase 2 trial to study the effectiveness and feasibility of association of trastuzumab with combination chemotherapy in advanced or metastatic bladder cancer patients. Combining monoclonal antibody therapy with combination chemotherapy may improve treatment efficacy on tumours overexpressed HER 2.


Eligibility criteria: Inclusion Criteria:

* Transitional cell carcinoma of the urothelium or bladder histologically proven stage IV AJCC \[locally advanced (T4b and / or N + M0) unresectable or metastatic (M1)\]
* Tumor and / or metastasis overexpressing HER2 immunohistochemistry (IHC 3 +) or IHC 2 + and FISH +. Centralized analysis.
* Measurable disease with at least one lesion with a diameter\> 2 cm for conventional methods (clinical examination, CT or MRI) or\> 1 cm for the helical scanner. In case of single metastasis, metastatic disease should be histologically proven
* Age ≥ 18 years and ≤80 years
* Life expectancy\> 3 months,
* Index performance status \<2 according to ECOG PS,
* No prior chemotherapy other than adjuvant and / or neoadjuvant chemotherapy, without Herceptin ® and complete for more than 6 months (naive to any previous chemotherapy in the metastatic setting)
* No radiotherapy within 4 weeks prior to inclusion,
* Normal cardiac function as measured by ejection fraction (LVEF\> 50%),
* Blood and liver satisfactory constants:

Hematological criteria: - Neutrophils\> 1.5 x 109 / L, - Chips\> 100 x 109 / L - Hemoglobin\> 10 g / dL, Liver function: - Alkaline phosphatase (unless bone metastases) \<2 x N - Total bilirubin \<1.5 x N - transaminases (AST, ALT) \<1.5 x N, renal Constants: - Creatinine clearance \> 30 ml / min (Cockcroft and Gault, cf. Annex XV protocol)

- Patient's written consent after full information.

Exclusion Criteria:

* Concurrent treatment with an experimental drug, participation in another clinical trial within \<30 days
* Patients previously treated with Herceptin ®, or another treatment targeting growth factors EGF (eg Iressa ®, Tarceva ®)
* Existence of a severe pulmonary disease, liver or kidney is likely to be exacerbated by the treatment,
* Other medical conditions: congestive heart failure or angina pectoris even if medically controlled failure, history of myocardial infarction before entering the trial, hypertension or uncontrolled arrhythmias, significant valvular disease,
* Patient with dyspnoea at rest or requiring oxygen therapy or with respiratory failure,
* Presence of a severe infection requiring antibiotics,
* Presence of CNS metastases or meningeal
* History of another malignancy uncured or cured for less than 5 years (except basal cell carcinoma, papillary thyroid carcinoma in situ of the cervix treated)
* Pregnant or lactating or not using effective contraception Women,
* For Cisplatin only: carrying a serious neurological disease, current events devices\> NCI grade 2 neuropathy, hearing loss, creatinine clearance \<60 ml / min, the patient can not support a patient hydration.

Primary outcomes:
measure: Progression Free survival
timeFrame: Participants will be followed from radomization until progression or death, up to 3 years
Secondary outcomes:
measure: Objective response rate
timeFrame: Objective Response Rate will be assessed during treatment period, every 3 cycles, up to 7 months
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Participants will be followed all along the study period, an expected average of 3 years
measure: Quality of life
timeFrame: Quality of Life will be assessed during the study period, every 3 cycles (Arm A patients) or every 3 months (Arm B patients), up to 3 years
measure: Overall survival
timeFrame: Participants will be followed from randomization until death or lost of follow-up, up to 3 years
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques saint Luc - Université Catholique de Louvain
city: Besançon
country: France
facility: CHU de Besançon
city: Bordeaux
country: France
facility: CHU Hôpital Saint André
city: Clermont Ferrand
country: France
facility: Hôpital Jean Perrin
city: La Roche-sur-yon
country: France
facility: Centre Hospitalier Départemental de la Vendée
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Marseille
country: France
facility: CHU Hôpital La Timone
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Neuilly-Sur-Seine
country: France
facility: Clinique Hartmann
city: Paris
country: France
facility: Curie Institute
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Groupe Hospitalier Saint Joseph Paris
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Suresnes
country: France
facility: Hôpital Foch
Study officials:
affiliation: Hôpital Européen Georges Pompidou, Paris (France)
name: Stéphane Oudard, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Curie Institute
name: Philippe Beuzeboc, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oudard S, Culine S, Vano Y, Goldwasser F, Theodore C, Nguyen T, Voog E, Banu E, Vieillefond A, Priou F, Deplanque G, Gravis G, Ravaud A, Vannetzel JM, Machiels JP, Muracciole X, Pichon MF, Bay JO, Elaidi R, Teghom C, Radvanyi F, Beuzeboc P. Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer. 2015 Jan;51(1):45-54. doi: 10.1016/j.ejca.2014.10.009. Epub 2014 Nov 15.