Efficacy of Combination of Trastuzumab to Gemcitabine - Platinum Advanced or Metastatic Urothelial Carcinoma

NCT ID: NCT01828736

Last Updated: 2017-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-09
• Study Completion Date: 2010-02-23

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.

Conditions

Recurrent Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Platinum + Gemcitabine

Gemcitabine = 1 000 mg/m2 Day1 and Day8 given every 21 days IV

+ If Creatinin Clearance > 60 ml/min : Cisplatin = Day 1: 70 mg/m² given every 21 days If Creatinin Clearance < 60 ml/min : Carboplatin = Day 1: AUC 5 given every 21 days

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days

Carboplatin

Intervention Type: DRUG

Given IV: AUC 5 on Day 1 every 21 days

Cisplatin

Intervention Type: DRUG

Given IV, 70 mg/m² BSA on day 1 every 21 days

Arm B: Platinum+Gemcitabine+Trastuzumab

Trastuzumab: Charging dose = 8mg/kg on day 1; then 6mg/kg every 21 days given IV + Gemcitabine = 1 000 mg/m2 Day1 and Day8 given every 21 days IV

+ If Creatinin Clearance > 60 ml/min : Cisplatin = Day 1: 70 mg/m² given every 21 days If Creatinin Clearance < 60 ml/min : Carboplatin = Day 1: AUC 5 given every 21 days

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: BIOLOGICAL

Bottles of 150 mg; Charging dose: 8mg/kg then 6mg/kg every 21 days given IV

Gemcitabine

Intervention Type: DRUG

Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days

Carboplatin

Intervention Type: DRUG

Given IV: AUC 5 on Day 1 every 21 days

Cisplatin

Intervention Type: DRUG

Given IV, 70 mg/m² BSA on day 1 every 21 days

Interventions

Trastuzumab

Bottles of 150 mg; Charging dose: 8mg/kg then 6mg/kg every 21 days given IV

Intervention Type: BIOLOGICAL

Gemcitabine

Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days

Intervention Type: DRUG

Carboplatin

Given IV: AUC 5 on Day 1 every 21 days

Intervention Type: DRUG

Cisplatin

Given IV, 70 mg/m² BSA on day 1 every 21 days

Intervention Type: DRUG

Other Intervention Names

anti-c-erB-2; Herceptin; MOAB HER2; dFdC; difluorodeoxycytidine hydrochloride; Gemzar; gemcitabin hydrochloride; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin; cis-Diamminedichloroplatinum(II); Platinum Diamminodichloride; Diamminodichloride, Platinum; cis-Platinum; cis Platinum; Dichlorodiammineplatinum; cis-Diamminedichloroplatinum; cis Diamminedichloroplatinum; cis-Dichlorodiammineplatinum(II); Platinol; Platidiam; Platino; NSC-119875; Biocisplatinum

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stéphane Oudard, MD, PhD.

Role: PRINCIPAL_INVESTIGATOR

Hôpital Européen Georges Pompidou, Paris (France)

Philippe Beuzeboc, MD

Role: PRINCIPAL_INVESTIGATOR

Curie Institute

Locations

Cliniques saint Luc - Université Catholique de Louvain

Brussels, , Belgium

CHU de Besançon

Besançon, , France

CHU Hôpital Saint André

Bordeaux, , France

Hôpital Jean Perrin

Clermont-Ferrand, , France

Centre Hospitalier Départemental de la Vendée

La Roche-sur-Yon, , France

Clinique Victor Hugo

Le Mans, , France

CHU Hôpital La Timone

Marseille, , France

Institut Paoli Calmettes

Marseille, , France

Clinique Hartmann

Neuilly-sur-Seine, , France

Curie Institute

Paris, , France

Hôpital Saint Louis

Paris, , France

Groupe Hospitalier Saint Joseph Paris

Paris, , France

Hôpital Cochin

Paris, , France

Hôpital Européen Georges Pompidou

Paris, , France

Hôpital Foch

Suresnes, , France

Countries

Belgium; France

References

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.

Reference Type: DERIVED

PMID: 25459391 (View on PubMed)

Other Identifiers

CVH-CT 02

Identifier Type: -

Identifier Source: org_study_id