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

Stage IV Bladder Cancer Clinical Trial

— CVH-CT02  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01828736
• Other study ID #: CVH-CT 02
• Status: Completed
• Phase: Phase 2
• First received: April 4, 2013
• Last updated: February 3, 2017
• Start date: February 9, 2004
• Est. completion date: February 23, 2010

Study information

• Verified date: February 2017
• Source: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: February 23, 2010
• Est. primary completion date: February 23, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Recurrent Bladder Cancer
• Stage IV Bladder Cancer
• Transitional Cell Carcinoma of the Bladder
• Urinary Bladder Neoplasms

Intervention

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

Drug:
• Gemcitabine
Given IV, 1000 mg/m² BSA on Day 1 and Day 8 every 21 days
• Carboplatin
Given IV: AUC 5 on Day 1 every 21 days
• Cisplatin
Given IV, 70 mg/m² BSA on day 1 every 21 days

Locations

Country	Name	City	State
Belgium	Cliniques saint Luc - Université Catholique de Louvain	Bruxelles
France	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	Groupe Hospitalier Saint Joseph Paris	Paris
France	Hôpital Cochin	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Saint Louis	Paris
France	Hôpital Foch	Suresnes

Sponsors (2)

Lead Sponsor	Collaborator
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie	Roche Pharma AG

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free survival		Participants will be followed from radomization until progression or death, up to 3 years
Secondary	Objective response rate		Objective Response Rate will be assessed during treatment period, every 3 cycles, up to 7 months
Secondary	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
Secondary	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
Secondary	Overall survival		Participants will be followed from randomization until death or lost of follow-up, up to 3 years