Efficacy of Combination of Trastuzumab to Gemcitabine - Platinum Advanced or Metastatic Urothelial Carcinoma (CVH-CT02)

Multicenter Randomized Phase 2 Trial of Gemcitabine - Platinum With or Without Trastuzumab in Advanced or Metastatic Urothelial Carcinoma With HER2 Overexpression

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder
• Intervention / Treatment: Drug: Gemcitabine; Drug: Carboplatin; Drug: Cisplatin; Biological: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques saint Luc - Université Catholique de Louvain
• France
  • Besançon, France, 25000
    • CHU de Besancon
  • Bordeaux, France, 33000
    • CHU Hôpital Saint André
  • Clermont Ferrand, France, 63000
    • Hôpital Jean Perrin
  • La Roche-sur-yon, France, 85000
    • Centre Hospitalier Départemental de la Vendée
  • Le Mans, France, 72000
    • Clinique Victor Hugo
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Marseille, France, 13005
    • CHU Hopital La Timone
  • Neuilly-Sur-Seine, France, 92200
    • Clinique Hartmann
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75010
    • Hôpital Saint Louis
  • Paris, France, 75014
    • Hopital Cochin
  • Paris, France, 75005
    • Curie Institute
  • Paris, France, 75014
    • Groupe Hospitalier Saint Joseph Paris
  • Suresnes, France, 92151
    • Hopital Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: Gemcitabine; Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days; Other Names: Gemzar; dFdC; difluorodeoxycytidine hydrochloride; gemcitabin hydrochloride; Drug: Carboplatin; Given IV: AUC 5 on Day 1 every 21 days; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Drug: Cisplatin; Given IV, 70 mg/m² BSA on day 1 every 21 days; Other Names: Platinol; Platinum Diamminodichloride; cis Platinum; cis-Diamminedichloroplatinum; cis-Diamminedichloroplatinum(II); Diamminodichloride, Platinum; cis-Platinum; Dichlorodiammineplatinum; cis Diamminedichloroplatinum; cis-Dichlorodiammineplatinum(II); Platidiam; Platino; NSC-119875; Biocisplatinum
Experimental: 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	Drug: Gemcitabine; Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days; Other Names: Gemzar; dFdC; difluorodeoxycytidine hydrochloride; gemcitabin hydrochloride; Drug: Carboplatin; Given IV: AUC 5 on Day 1 every 21 days; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Drug: Cisplatin; Given IV, 70 mg/m² BSA on day 1 every 21 days; Other Names: Platinol; Platinum Diamminodichloride; cis Platinum; cis-Diamminedichloroplatinum; cis-Diamminedichloroplatinum(II); Diamminodichloride, Platinum; cis-Platinum; Dichlorodiammineplatinum; cis Diamminedichloroplatinum; cis-Dichlorodiammineplatinum(II); Platidiam; Platino; NSC-119875; Biocisplatinum; Biological: Trastuzumab; Bottles of 150 mg; Charging dose: 8mg/kg then 6mg/kg every 21 days given IV; Other Names: Herceptin; anti-c-erB-2; MOAB HER2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free survival	Participants will be followed from radomization until progression or death, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate		Objective Response Rate will be assessed during treatment period, every 3 cycles, up to 7 months
Number of participants with adverse events as a measure of safety and tolerability	Toxicity will be classify according to NCI-CTC criteria Version 2.0. Cardiac toxicity will be assessed according to the NYHA (New York Heart Association) criteria.	Participants will be followed all along the study period, an expected average of 3 years
Quality of life	Quality of Life will be assessed according to the EORTC QLQ-C30 Version 3 questionnaire	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
Overall survival		Participants will be followed from randomization until death or lost of follow-up, up to 3 years

Collaborators and Investigators

• Sponsor: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Stéphane Oudard, MD, PhD., Hôpital Européen Georges Pompidou, Paris (France); Principal Investigator: Philippe Beuzeboc, MD, Curie Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2004
• Primary Completion (Actual): February 23, 2010
• Study Completion (Actual): February 23, 2010

Study Registration Dates

• First Submitted: April 4, 2013
• First Submitted That Met QC Criteria: April 8, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Estimate): February 6, 2017
• Last Update Submitted That Met QC Criteria: February 3, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Treatment; Trastuzumab; Urothelial carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Gemcitabine; Carboplatin; Trastuzumab; Cisplatin
• Other Study ID Numbers: CVH-CT 02