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

NCT01828736 | Completed Phase 2

• 1 other identifier: CVH-CT 02
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 15

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

Keywords

Urothelial carcinoma; Trastuzumab; Treatment

Outcome Measures

Primary Outcomes (1)

• Progression Free survival

  Participants will be followed from radomization until progression or death, up to 3 years

Secondary Outcomes (4)

• 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

  Participants will be followed all along the study period, an expected average of 3 years

• Quality of life

  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

Study Arms (2)

Arm A: Platinum + Gemcitabine

ACTIVE COMPARATOR

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; Drug: Carboplatin; Drug: Cisplatin

Arm B: Platinum+Gemcitabine+Trastuzumab

EXPERIMENTAL

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

Biological: Trastuzumab; Drug: Gemcitabine; Drug: Carboplatin; Drug: Cisplatin

Interventions

Trastuzumab BIOLOGICAL

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

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

Arm B: Platinum+Gemcitabine+Trastuzumab

Gemcitabine DRUG

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

Also known as: dFdC, difluorodeoxycytidine hydrochloride, Gemzar, gemcitabin hydrochloride

Arm A: Platinum + Gemcitabine; Arm B: Platinum+Gemcitabine+Trastuzumab

Carboplatin DRUG

Given IV: AUC 5 on Day 1 every 21 days

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Arm A: Platinum + Gemcitabine; Arm B: Platinum+Gemcitabine+Trastuzumab

Cisplatin DRUG

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

Also known as: 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

Arm A: Platinum + Gemcitabine; Arm B: Platinum+Gemcitabine+Trastuzumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie: lead
• Roche Pharma AG: collaborator

Study Sites (15)

Cliniques saint Luc - Université Catholique de Louvain

Brussels, 1200, Belgium

Location

CHU de Besançon

Besançon, 25000, France

Location

CHU Hôpital Saint André

Bordeaux, 33000, France

Location

Hôpital Jean Perrin

Clermont-Ferrand, 63000, France

Location

Centre Hospitalier Départemental de la Vendée

La Roche-sur-Yon, 85000, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

CHU Hôpital La Timone

Marseille, 13005, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Clinique Hartmann

Neuilly-sur-Seine, 92200, France

Location

Curie Institute

Paris, 75005, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Groupe Hospitalier Saint Joseph Paris

Paris, 75014, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Hôpital Foch

Suresnes, 92151, France

Location

Related Publications (1)

• 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.

  PMID: 25459391 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Trastuzumab; Gemcitabine; Carboplatin; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Stéphane Oudard, MD, PhD.

  Hôpital Européen Georges Pompidou, Paris (France)

  PRINCIPAL INVESTIGATOR

• Philippe Beuzeboc, MD

  Curie Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: April 11, 2013
• Study Start: February 9, 2004
• Primary Completion: February 23, 2010
• Study Completion: February 23, 2010
• Last Updated: February 6, 2017

Record last verified: 2017-02

Locations

BE (1); FR (14)