A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.

NCT02240017 | Completed Phase 2

• 1 other identifier: 13 URO 02
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 18

Brief Summary

This is a phase II/III, multicenter, randomized study which includes 420 patients on six years + 3 years follow up. 92 patients will be included during the phase II ; additional 328 patients will be included. Patients with an advanced or metastatic urothelial cancer with impaired renal function will be randomized in one of the two following chemotherapy arm:

• Fractionated Cisplatin + Gemcitabine.
• Carboplatin + Gemcitabine. The main objective of the part II study will be to evaluate the efficacy and the safety of a chemotherapy with a doublet platinum salt compound/Gemcitabine with fractionated Cisplatin or Carboplatin in this population. The main objective of the part III study will be to compare the efficacy in terms of overall survival of a chemotherapy with a doublet platinum salt/Gemcitabine with fractionated Cisplatin or Carboplatin in this population.

Conditions

Advanced Urothelial Cancer; Metastatic Urothelial Cancer

Keywords

Urothelial cancer, renal function impaired.

Outcome Measures

Primary Outcomes (3)

• Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21).

  Progression is defined according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria V1.1.

  5 years.

• Phase III: Overall survival (in months).

  Overall survival is defined as the time from randomization until death or last follow up news (censured data).

  9 years.

• Phase II: Tolerance - Percentage of patients for whom at least one of the 3 defined tolerance criteria (see description) is observed.

  Defined tolerance criteria : * Postponement of chemotherapy \> or = 2 weeks. * Alteration of renal function. * Need to decrease twice Gemcitabine dose on day 1 for : NCI CTC (National Cancer Institut Common Toxicity Criteria) grade III or IV non-hematologic toxicity, hematologic toxicity.

  5 years.

Secondary Outcomes (9)

• Phase II and III: Objective response.

  Phase II: 5 years ; Phase III: 9 years.

• Phase II and III: Tolerance according to NCI toxicity scale (version 4.0).

  Phase II: 5 years ; Phase III: 9 years.

• Phase II and III: Geriatric evaluation using questionnaires.

  Phase II: 5 years ; Phase III: 9 years.

• Phase II and III: Quality of life using the EORTC QLQ - C30 questionnaire (European Organization for research and treatment of Cancer - Quality of life questionnaire).

  Phase II: 5 years ; Phase III: 9 years.

• Phase II and III: Pharmacokinetics - Platin concentrations

  At cycles 1 and 2 day 1 - 5 mn before the end of infusion, one hour after the end of infusion, 3 hours (arm A) or 4 hours (arm B) after the end of infusion.

Study Arms (2)

Carboplatin/Gemcitabine

ACTIVE COMPARATOR

Drug: Carboplatin; Drug: Gemcitabine

Fractionated Cisplatin/Gemcitabine

EXPERIMENTAL

Drug: Fractionated Cisplatin; Drug: Gemcitabine

Interventions

Carboplatin DRUG

Carboplatin AUC (area under curve) 4,5 at day 1 of each cycle until 6 cycles.

Carboplatin/Gemcitabine

Fractionated Cisplatin DRUG

Cisplatin 35mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Fractionated Cisplatin/Gemcitabine

Gemcitabine DRUG

Gemcitabine 1000mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Carboplatin/Gemcitabine; Fractionated Cisplatin/Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Age \< or = 18 years, patients aged 75 years or more will benefit from a geriatric assessment.
• Advanced or metastatic urothelial cancer confirmed histologically or cytologically.
• Patients liable to receive a first -line chemotherapy for advanced or metastatic urothelial carcinoma.
• Measurable disease according to RECIST criteria V1.1.
• Patients who received neoadjuvant or adjuvant chemotherapy based on platinum salt must have completed treatment at least 6 months before entering the study.
• Performance status \< or = 2.
• Life expectancy \> 3 months.
• Patients with creatinine clearance between 40 and 60 ml / min ( according to Cockcroft and Gault ).
• Patients having no contra-indication to overhydration.
• Satisfactory hematological tests: Neutrophils \> 1.5 G / l Platelets \> 150 G / l , hemoglobin ≥ 10 g / dl.
• Satisfactory liver function tests: total bilirubin \< 1.5 x ULN (upper limit of normal), AST (aspartate aminotransferase) and ALT (alanine aminotransferase)\<or = 2.5 x ULN (or 5 x ULN if liver metastases).
• In case of prior radiotherapy, a minimum of 14 days must relapse between the end of radiotherapy and study entry.
• For women of childbearing age , use an effective contraceptive method to study entry and for the duration of the study and 6 months after the last dose of study treatment ; For sexually active fertile men having a partner of childbearing age using effective contraception for the duration of the study and 6 months after the last dose of study treatment.
• Patient affiliated to a social security system in France.

You may not qualify if:

• Any concomitant or previous malignancy within 5 years prior to the study ( with the exception of basal cell or squamous cell carcinoma in situ).
• Pregnant or lactating women.
• Patients with brain metastases or meningeal or symptoms suggestive of such secondary locations.
• Bisphosphonate or Denosumab treatment initiated within 28 days prior to randomization into the study or patient who have started such treatment during the study ( a bisphosphonate or denosumab treatment initiated within a period longer than 28 days before randomization may be continued without change during the study ).
• Other concomitant cancer (radiation therapy, radiopharmaceutical agent chemotherapy).
• Patients with uncontrolled infection.
• Patients with peripheral neuropathy grade\> 1, whatever the origin or patients with hearing loss.
• Patient with unstable disease (eg: unstable diabetes, poorly controlled hypertension , congestive heart failure or myocardial infarction within 3 months prior to study entry).
• Known hypersensitivity to study drugs.
• Any psychological condition , familial, sociological or geographical not to comply with medical monitoring and / or procedures in the study protocol.
• Patient protected by law.

Sponsors & Collaborators

• Institut Claudius Regaud: lead

Study Sites (18)

INSTITUT DE CANCEROLOGIE DE L'OUEST - Site Paul Papin

Angers, 49933, France

Location

Chru Besancon - Hopital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

CH VERSAILLES - Hôpital André Mignot

Le Chesnay, 78157, France

Location

CHU LIMOGES - Hôpital Dupuytren

Limoges, 87042, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Ch Mont de Marsan

Mont-de-Marsan, 40024, France

Location

Institut Regional Du Cancer Montpellier

Montpellier, 34298, France

Location

Ap-Hp-Hopital Saint-Louis

Paris, 75010, France

Location

INSTITUT DE CANCEROLOGIE DE L'OUEST - Site René Gauducheau

Saint-Herblain, 44805, France

Location

Institut de Cancerologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42271, France

Location

CHU de STRASBOURG

Strasbourg, 67091, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Chru Tours

Tours, 37044, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Interventions

Carboplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Loic MOUREY, MD

  Institut Claudius Regaud

  STUDY CHAIR

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: September 5, 2014
• First Posted: September 15, 2014
• Study Start: January 21, 2015
• Primary Completion: April 10, 2018
• Study Completion: July 15, 2019
• Last Updated: August 9, 2019

Record last verified: 2019-08

Locations

FR (18)