Clinical trial NCT02001272: EWOC-1 Trial: Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer
Official title: EWOC-1 Trial: Multicenter, Randomized Trial of Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Elderly
Vulnerable
Ovarian cancer
Chemotherapy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2013-12-04
Enrollment: 120
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current standard of first-line chemotherapy in advanced ovarian cancer is the combination of carboplatin AUC 5mg/mL/min and paclitaxel 175 mg.m-². This combination is feasible in selected elderly patients such as those included in prospective trials. These trials, however, include a minority of the elderly population. In wider selection of patients \>70 years old, the standard carboplatin-paclitaxel regimen has been shown to induce an excess of toxicity and premature treatment stopping. For elderly patients thought to be vulnerable and at high risk of toxicity with the standard 3-weekly carboplatin-paclitaxel regimen, other options are used in routine practice. One option is to delete paclitaxel and treat elderly patients with carboplatin as a single agent. An alternative is to use the carboplatin-paclitaxel regimen in a weekly schedule for both drugs such as reported by the MITO (Multicentre Italian Trial in Ovarian Cancer).

To date, there is no randomized trial which could give us some evidence of how to select patients who could benefit most of one or the other regimen described above. The 4th Ovarian Cancer Consensus Conference has indeed recognised the medical unmet need of adapted therapy for elderly patients with ovarian cancer and the necessity of additional research in this population.

Recently, GINECO has described a Geriatric Vulnerability Score (GVS) in a population of elderly patients with advanced ovarian cancer included in a specific multicenter phase II trial. The best proportional hazard model fitting for overall survival identified the following geriatric covariates score as being poor survival risk factors: ADL score \<6, IADL score \<25, HADS score \>14, albuminemia \<35g/L and , lymphopenia \<1G/L. GVS is the sum of these risk factors for each patient. Using a cut off of 3, the GVS identified a group of patients at high risk of severe toxicity, early cessation of treatment, unplanned hospitalization and adverse outcomes.

This international multicentre randomized phase II trial will compare the success rate of delivering 6 courses of chemotherapy with evidence of efficacy and without premature termination for progression, death or unacceptable toxicity of three different chemotherapy regimens in a selected population of elderly patients with a GVS ≥ 3:

* Arm A: Paclitaxel 175mg/m²/3 hours, I.V. and carboplatin AUC 5, I.V. every 3 weeks
* Arm B: Carboplatin monotherapy AUC 5 or 6 every 3 weeks
* Arm C: Weekly paclitaxel 60 mg/m²/1 hour and weekly carboplatin AUC 2 (d1, d8, d15 every 4 weeks)

The total number of patients to be enrolled is 240, ie 22 in each arm (total = 66) at the first step, then 58 more by arm (total=174) after interim analysis.


Eligibility criteria: Inclusion Criteria:

* Woman \>70 year old
* Histologically or cytologically proven FIGO stage III to IV epithelial ovarian cancer or peritoneal primary or fallopian tube. A cytological proof is accepted if associated with a ratio of CA125/CEA \>25 and a radiological pelvic mass.
* GVS (Geriatric Vulnerability Score) \>3.
* Adequate bone marrow function including the following: Neutrophils ≥ 1.5 x 109/L , platelets ≥100 x 109/L and hemoglobin ≥9 g/dL.
* Adequate glomerular filtration rate \>40 ml/min (estimates based on MDRD or Chatelut formula are sufficient)
* No icterus.
* Life expectancy \> 3 months.
* Written informed consent obtained.
* Covered by a Health System where applicable

Exclusion Criteria:

* Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
* Prior history of chemotherapy.
* Prior history of radiotherapy which may affect patient tolerability to chemotherapy.
* Major perturbations of liver biology: Bilirubin \> 2 fold the upper normal limit (UNL), SGOT-SGPT \> 3 fold UNL.
* Patient unable to be regularly followed for any reason (geographic, familial, social, psychologic).
* Any mental or physical handicap at risk of interfering with the appropriate treatment.
* Known allergy to Cremophor ® EL -containing drugs.
* Any administrative or legal supervision where applicable

Primary outcomes:
measure: Treatment success.Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity
timeFrame: After 6 courses of chemotherapy i.e 4.5 to 6 months (depending on the arm)
Secondary outcomes:
measure: Therapeutical strategy
timeFrame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
measure: Overall Survival
timeFrame: 2.5 years
measure: Progression-free survival
timeFrame: 2.5 years
measure: Quality of Life
timeFrame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
measure: Safety and tolerability
timeFrame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
measure: Aging biomarkers
timeFrame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Notre-Dame Hospital of the CHUM
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Alès
country: France
facility: Service d'Oncologie Médicale - Centre Hospitalier d'Alès
city: Angers
country: France
facility: Service d'Oncologie Médicale - ICO Paul Papin
city: Avignon Cedex 9
country: France
facility: Service de cancérologie clinique - Institut Sainte-Catherine
city: Besançon
country: France
facility: Servide d'Oncologie Médicale - Hôpital Jean Minjoz
city: Bordeaux Cedex
country: France
facility: Service d'Oncologie Médicale - Institut Bergonié
city: Bourg en Bresse
country: France
facility: Service d'Onco-Hématologie - Hôpital Fleyriat
city: Brest
country: France
facility: Service de Radiothérapie et Oncologie Médicale - Hôpital Morvan
city: Caen Cedex 5
country: France
facility: Service d'Uro-Gynécologie - Centre François Baclesse
city: Chambéry
country: France
facility: Service d'Oncologie - Centre Hospitalier de Chambéry
city: Cholet
country: France
facility: Service d'Oncologie Médicale - Centre Hospitalier de Cholet
city: Clermont-Ferrand
country: France
facility: Servide d'Oncologie Médicale - Centre Jean Perrin
city: Contamines Sur Arve
country: France
facility: Service d'Oncologie - Centre Hospitalier Alpes Leman
city: Créteil Cedex
country: France
facility: Service d'Oncologie Radiothérapie - Centre Hospitalier Intercommunal de Créteil
city: Dijon
country: France
facility: Service d'Oncologie Médicale - Centre d'Oncologie et de Radiothérapie du Parc
city: Dijon
country: France
facility: Service d'Oncologie Médicale - Centre Georges François Leclerc
city: Gap
country: France
facility: Service de Médecine Gériatrique - Centre Hospitalier Intercommunal des Alpes du Sud -Site de Gap
city: Grenoble
country: France
facility: Service d'Oncologie Médicale - Hôpital Michallon - CHU Grenoble
city: Le Chesnay Cedex
country: France
facility: Service d''Hématologie Oncologie - Hôpital André Mignot
city: Le Mans
country: France
facility: Service d'Oncologie Médicale - Centre Jean Bernard - Clinique Victor Hugo
city: Le Mans
country: France
facility: Service de Médecine Interne et Oncologie Médicale - CH du Mans
city: Limoges
country: France
facility: Service d'Oncologie - Hôpital Dupuytren
city: Lyon Cedex 08
country: France
facility: Service d'Oncologie Service 2 B Nord - Centre Léon Bérard
city: Marseille Cedex 20
country: France
facility: Service d'Oncologie multidisciplinaire - Hôpital Nord
city: Marseille Cedex 9
country: France
facility: Service d'Oncologie Médicale - Institut Paoli Calmettes
city: Montpellier Cedex 5
country: France
facility: Service d'Oncologie Médicale - Institut Régional du Cancer Montpellier, Val d'Aurelle
city: Mougins Cedex 02
country: France
facility: Service d'Oncologie Médicale - Centre Azuréen de Cancérologie
city: Nantes Cedex 2
country: France
facility: Service de Chimiothérapie - Centre Catherine de Sienne
city: Nice Cedex 2
country: France
facility: Service d'Onco-Hématologie - Centre Antoine Lacassagne
city: Nîmes
country: France
facility: Service d'Oncologie Radiothérapie - Clinique de Valdegour
city: Orléans Cedex 02
country: France
facility: Servicde d'Oncologie Médicale - Centre Hospitalier Régional d'Orléans
city: Paris Cedex 12
country: France
facility: Service d'Oncologie Médicale - Hôpital des Diaconesses
city: Paris Cedex 14
country: France
facility: Service d'Oncologie - Hôpital Cochin
city: Paris Cedex 15
country: France
facility: Service d'Oncologie Médicale - Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Service d'Oncologie - Groupe Hospitalier Saint-Joseph
city: Perpignan
country: France
facility: Service d'Oncologie Médicale - Centre Hospitalier de Perpignan
city: Pierre-Bénite
country: France
facility: Service oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon
city: Plerin Sur Mer
country: France
facility: Centre CARIO - Hôpital Privé des Côtes d'Armor
city: Pringy Cedex
country: France
facility: Servide d'Oncologie Médicale - Centre Hospitalier de la Région d'Annecy
city: Quimper Cedex
country: France
facility: Servide de Radiothérapie et Oncologie Médicale - Centre Hospitalier Intercommunal de Cornouaille
city: Reims Cedex
country: France
facility: Servide d'Oncologie Médicale - Institut Jean Godinot
city: Saint Brieuc
country: France
facility: Service d'Oncologie Médicale - Centre Hospitalier Yves le Foll
city: Saint Herblain
country: France
facility: Service d'Oncologie Médicale - ICO Centre René Gauducheau
city: Saint Malo
country: France
facility: service d'Oncologie Médicale - Centre Hospitalier Broussais
city: Saint Mandé
country: France
facility: Service de Médecine interne et oncologie - Hôpital Inter Armées de Begin
city: Saint Nazaire
country: France
facility: Service d'Oncologie Médicale - Clinique Mutualiste de l'Estuaire, Cité Sanitaire
city: Saint-Grégoire
country: France
facility: Service d'Oncologie Radiothérapie - Centre Hospitalier Privé de Saint-Grégoire
city: Senlis
country: France
facility: Service d'Oncologie Médicale - Groupe Hospitalier Public du Sud de l'Oise - Site de Senlis
city: Sens
country: France
facility: Service d'Oncologie Médicale - Centre Hospitalier de Sens
city: Strasbourg
country: France
facility: Service d'Oncologie Médicale - Centre Paul Strauss
city: Thonon les Bains
country: France
facility: Service de Chirurgie et Oncologie Gynécologique et Mammaire - Hôpitaux du Léman
city: Toulouse
country: France
facility: Service d'Oncologie Médicale - Institut Claudius Regaud
city: Vandoeuvre lès Nancy
country: France
facility: Service d'Oncologie Médicale - Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Service de Médecine Oncologique - Institut de Cancérologie Gustave Roussy
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - CRO,IRCCS
city: Legnago
country: Italy
facility: Azienda Ulss 21 Legnago
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
city: Mirano
country: Italy
facility: Ulls13 - Mirano
city: Sassuolo
country: Italy
facility: Ospedale Nuovo di Sassuolo
city: Torino
country: Italy
facility: Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo
city: Linköping
country: Sweden
facility: Linköping University Hospital
Study officials:
affiliation: Service d'oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon
name: Claire FALANDRY, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Falandry C, Rousseau F, Mouret-Reynier MA, Tinquaut F, Lorusso D, Herrstedt J, Savoye AM, Stefani L, Bourbouloux E, Sverdlin R, D'Hondt V, Lortholary A, Brachet PE, Zannetti A, Malaurie E, Venat-Bouvet L, Tredan O, Mourey L, Pujade-Lauraine E, Freyer G; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire et du sein (GINECO). Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer: A GINECO/GCIG Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):853-861. doi: 10.1001/jamaoncol.2021.0696.