EWOC-1 Trial: Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer

Ovarian Cancer Clinical Trial

— EWOC-1  

Official title:

EWOC-1 Trial: Multicenter, Randomized Trial of Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02001272
• Other study ID #: 2012-772
• Status: Completed
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: February 2020

Study information

• Verified date: February 2020
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Paclitaxel + Carboplatin every 3 weeks
Patients will receive a premedication of 130mg prednisolone the day before (22 pm) and the morning (7 am). A pretreatment using corticosteroids, antihistamines and H2 antagonists and setrons in accordance with local standards of care will be administered 30 minutes before Paclitaxel administration. At H0, Paclitaxel is administered at 175mg/m² in 3 hours then Carboplatin is administered at AUC 5mg/mL/min.
• Carboplatin monotherapy every 3 weeks
A pretreatment using setrons in accordance with local standards of care will be administered 30 minutes before Carboplatin at AUC 5 to 6mg/mL/min in 1 hour.
• Weekly Paclitaxel and Carboplatin
A pretreatment using corticosteroids, antihistamines and H2 antagonists and setrons in accordance with local standards of care will be administered 30 minutes before Paclitaxel 60mg/m² in 1 hour followed by Carboplatin at AUC 2mg/mL/min in 1 hour.

Locations

Country	Name	City	State
Canada	Notre-Dame Hospital of the CHUM	Montréal
Denmark	Herlev Hospital	Herlev
Finland	Kuopio University Hospital	Kuopio
France	Service d'Oncologie Médicale - Centre Hospitalier d'Alès	Alès
France	Service d'Oncologie Médicale - ICO Paul Papin	Angers
France	Service de cancérologie clinique - Institut Sainte-Catherine	Avignon Cedex 9
France	Servide d'Oncologie Médicale - Hôpital Jean Minjoz	Besançon
France	Service d'Oncologie Médicale - Institut Bergonié	Bordeaux Cedex
France	Service d'Onco-Hématologie - Hôpital Fleyriat	Bourg en Bresse
France	Service de Radiothérapie et Oncologie Médicale - Hôpital Morvan	Brest
France	Service d'Uro-Gynécologie - Centre François Baclesse	Caen Cedex 5
France	Service d'Oncologie - Centre Hospitalier de Chambéry	Chambéry
France	Service d'Oncologie Médicale - Centre Hospitalier de Cholet	Cholet
France	Servide d'Oncologie Médicale - Centre Jean Perrin	Clermont-Ferrand
France	Service d'Oncologie - Centre Hospitalier Alpes Leman	Contamines Sur Arve
France	Service d'Oncologie Radiothérapie - Centre Hospitalier Intercommunal de Créteil	Créteil Cedex
France	Service d'Oncologie Médicale - Centre d'Oncologie et de Radiothérapie du Parc	Dijon
France	Service d'Oncologie Médicale - Centre Georges François Leclerc	Dijon
France	Service de Médecine Gériatrique - Centre Hospitalier Intercommunal des Alpes du Sud -Site de Gap	Gap
France	Service d'Oncologie Médicale - Hôpital Michallon - CHU Grenoble	Grenoble
France	Service d''Hématologie Oncologie - Hôpital André Mignot	Le Chesnay Cedex
France	Service d'Oncologie Médicale - Centre Jean Bernard - Clinique Victor Hugo	Le Mans
France	Service de Médecine Interne et Oncologie Médicale - CH du Mans	Le Mans
France	Service d'Oncologie - Hôpital Dupuytren	Limoges
France	Service d'Oncologie Service 2 B Nord - Centre Léon Bérard	Lyon Cedex 08
France	Service d'Oncologie multidisciplinaire - Hôpital Nord	Marseille Cedex 20
France	Service d'Oncologie Médicale - Institut Paoli Calmettes	Marseille Cedex 9
France	Service d'Oncologie Médicale - Institut Régional du Cancer Montpellier, Val d'Aurelle	Montpellier Cedex 5
France	Service d'Oncologie Médicale - Centre Azuréen de Cancérologie	Mougins Cedex 02
France	Service de Chimiothérapie - Centre Catherine de Sienne	Nantes Cedex 2
France	Service d'Onco-Hématologie - Centre Antoine Lacassagne	Nice Cedex 2
France	Service d'Oncologie Radiothérapie - Clinique de Valdegour	Nîmes
France	Servicde d'Oncologie Médicale - Centre Hospitalier Régional d'Orléans	Orléans Cedex 02
France	Service d'Oncologie - Groupe Hospitalier Saint-Joseph	Paris
France	Service d'Oncologie Médicale - Hôpital des Diaconesses	Paris Cedex 12
France	Service d'Oncologie - Hôpital Cochin	Paris Cedex 14
France	Service d'Oncologie Médicale - Hôpital Européen Georges Pompidou	Paris Cedex 15
France	Service d'Oncologie Médicale - Centre Hospitalier de Perpignan	Perpignan
France	Service oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon	Pierre-Bénite
France	Centre CARIO - Hôpital Privé des Côtes d'Armor	Plerin Sur Mer
France	Servide d'Oncologie Médicale - Centre Hospitalier de la Région d'Annecy	Pringy Cedex
France	Servide de Radiothérapie et Oncologie Médicale - Centre Hospitalier Intercommunal de Cornouaille	Quimper Cedex
France	Servide d'Oncologie Médicale - Institut Jean Godinot	Reims Cedex
France	Service d'Oncologie Médicale - Centre Hospitalier Yves le Foll	Saint Brieuc
France	Service d'Oncologie Médicale - ICO Centre René Gauducheau	Saint Herblain
France	service d'Oncologie Médicale - Centre Hospitalier Broussais	Saint Malo
France	Service de Médecine interne et oncologie - Hôpital Inter Armées de Begin	Saint Mandé
France	Service d'Oncologie Médicale - Clinique Mutualiste de l'Estuaire, Cité Sanitaire	Saint Nazaire
France	Service d'Oncologie Radiothérapie - Centre Hospitalier Privé de Saint-Grégoire	Saint-Grégoire
France	Service d'Oncologie Médicale - Groupe Hospitalier Public du Sud de l'Oise - Site de Senlis	Senlis
France	Service d'Oncologie Médicale - Centre Hospitalier de Sens	Sens
France	Service d'Oncologie Médicale - Centre Paul Strauss	Strasbourg
France	Service de Chirurgie et Oncologie Gynécologique et Mammaire - Hôpitaux du Léman	Thonon les Bains
France	Service d'Oncologie Médicale - Institut Claudius Regaud	Toulouse
France	Service d'Oncologie Médicale - Institut de Cancérologie de Lorraine	Vandoeuvre lès Nancy
France	Service de Médecine Oncologique - Institut de Cancérologie Gustave Roussy	Villejuif
Italy	Centro di Riferimento Oncologico - CRO,IRCCS	Aviano
Italy	Azienda Ulss 21 Legnago	Legnago
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milano
Italy	Ulls13 - Mirano	Mirano
Italy	Ospedale Nuovo di Sassuolo	Sassuolo
Italy	Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo	Torino
Sweden	Linköping University Hospital	Linköping

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Countries where clinical trial is conducted

Canada,  Denmark,  Finland,  France,  Italy,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment success.Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity	Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity. Unacceptable toxicity is defined as a major adverse event related to chemotherapy or treatment procedure leading either to early treatment stopping, to an unplanned hospital admission or to death or to a dose delay lasting more than 14 days or more than 2 dose reductions.	After 6 courses of chemotherapy i.e 4.5 to 6 months (depending on the arm)
Secondary	Therapeutical strategy	Therapeutical strategy will be assessed by measuring the feasibility of performing an optimal surgery and feasibility of performing neoadjuvant chemotherapy and surgery and post operative chemotherapy until 6 courses in case of planned interval debulking surgery.	At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
Secondary	Overall Survival	Overall survival is defined as the time period from the date of randomization to the date of death.	2.5 years
Secondary	Progression-free survival	Progression-free survival is defined as the time period from the date of randomization to the date of disease progression or death whichever occurs first.	2.5 years
Secondary	Quality of Life	Quality of life is evaluated using the FACT-O questionnaire	At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
Secondary	Safety and tolerability	Adverse events are defined using the NCI-CTC AE scale version 4.3	At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
Secondary	Aging biomarkers	Aging biomarkers are represented by the expression level of cathelin-related antimicrobial peptide or CRAMP, stathmin, EF-1a, and chitinase	At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)

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