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

August 3, 2020 updated by: Hospices Civils de Lyon

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Montréal, Canada
        • Notre-Dame Hospital of the CHUM
  • Denmark
      • Herlev, Denmark
        • Herlev Hospital
  • Finland
      • Kuopio, Finland
        • Kuopio University Hospital
  • France
      • Alès, France, 30100
        • Service d'Oncologie Médicale - Centre Hospitalier d'Alès
      • Angers, France, 49100
        • Service d'Oncologie Médicale - ICO Paul Papin
      • Avignon Cedex 9, France, 84918
        • Service de cancérologie clinique - Institut Sainte-Catherine
      • Besançon, France, 25030
        • Servide d'Oncologie Médicale - Hôpital Jean Minjoz
      • Bordeaux Cedex, France, 33076
        • Service d'Oncologie Médicale - Institut Bergonié
      • Bourg en Bresse, France, 01012
        • Service d'Onco-Hématologie - Hôpital Fleyriat
      • Brest, France, 29200
        • Service de Radiothérapie et Oncologie Médicale - Hôpital Morvan
      • Caen Cedex 5, France, 14076
        • Service d'Uro-Gynécologie - Centre François Baclesse
      • Chambéry, France, 73011
        • Service d'Oncologie - Centre Hospitalier de Chambéry
      • Cholet, France, 49300
        • Service d'Oncologie Médicale - Centre Hospitalier de Cholet
      • Clermont-Ferrand, France, 63000
        • Servide d'Oncologie Médicale - Centre Jean Perrin
      • Contamines Sur Arve, France, 74130
        • Service d'Oncologie - Centre Hospitalier Alpes Leman
      • Créteil Cedex, France, 94010
        • Service d'Oncologie Radiothérapie - Centre Hospitalier Intercommunal de Créteil
      • Dijon, France, 21000
        • Service d'Oncologie Médicale - Centre d'Oncologie et de Radiothérapie du Parc
      • Dijon, France, 21079
        • Service d'Oncologie Médicale - Centre Georges François Leclerc
      • Gap, France, 05000
        • Service de Médecine Gériatrique - Centre Hospitalier Intercommunal des Alpes du Sud -Site de Gap
      • Grenoble, France, 38043
        • Service d'Oncologie Médicale - Hôpital Michallon - CHU Grenoble
      • Le Chesnay Cedex, France, 78157
        • Service d''Hématologie Oncologie - Hôpital André Mignot
      • Le Mans, France, 72000
        • Service d'Oncologie Médicale - Centre Jean Bernard - Clinique Victor Hugo
      • Le Mans, France, 72000
        • Service de Médecine Interne et Oncologie Médicale - CH du Mans
      • Limoges, France, 87042
        • Service d'Oncologie - Hôpital Dupuytren
      • Lyon Cedex 08, France, 69373
        • Service d'Oncologie Service 2 B Nord - Centre Léon Bérard
      • Marseille Cedex 20, France, 13915
        • Service d'Oncologie multidisciplinaire - Hôpital Nord
      • Marseille Cedex 9, France, 13273
        • Service d'Oncologie Médicale - Institut Paoli Calmettes
      • Montpellier Cedex 5, France, 34298
        • Service d'Oncologie Médicale - Institut Régional du Cancer Montpellier, Val d'Aurelle
      • Mougins Cedex 02, France, 06250
        • Service d'Oncologie Médicale - Centre Azuréen de Cancérologie
      • Nantes Cedex 2, France, 44202
        • Service de Chimiothérapie - Centre Catherine de Sienne
      • Nice Cedex 2, France, 06186
        • Service d'Onco-Hématologie - Centre Antoine Lacassagne
      • Nîmes, France, 30900
        • Service d'Oncologie Radiothérapie - Clinique de Valdegour
      • Orléans Cedex 02, France, 45067
        • Servicde d'Oncologie Médicale - Centre Hospitalier Régional d'Orléans
      • Paris, France, 75674
        • Service d'Oncologie - Groupe Hospitalier Saint-Joseph
      • Paris Cedex 12, France, 75012
        • Service d'Oncologie Médicale - Hôpital des Diaconesses
      • Paris Cedex 14, France, 75014
        • Service d'Oncologie - Hôpital Cochin
      • Paris Cedex 15, France, 75908
        • Service d'Oncologie Médicale - Hôpital Européen Georges Pompidou
      • Perpignan, France, 66046
        • Service d'Oncologie Médicale - Centre Hospitalier de Perpignan
      • Pierre-Bénite, France, 69495
        • Service oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon
      • Plerin Sur Mer, France, 22190
        • Centre CARIO - Hôpital Privé des Côtes d'Armor
      • Pringy Cedex, France, 74374
        • Servide d'Oncologie Médicale - Centre Hospitalier de la Région d'Annecy
      • Quimper Cedex, France, 29107
        • Servide de Radiothérapie et Oncologie Médicale - Centre Hospitalier Intercommunal de Cornouaille
      • Reims Cedex, France, 51056
        • Servide d'Oncologie Médicale - Institut Jean Godinot
      • Saint Brieuc, France, 22015
        • Service d'Oncologie Médicale - Centre Hospitalier Yves le Foll
      • Saint Herblain, France, 44805
        • Service d'Oncologie Médicale - ICO Centre René Gauducheau
      • Saint Malo, France, 35403
        • service d'Oncologie Médicale - Centre Hospitalier Broussais
      • Saint Mandé, France, 94163
        • Service de Médecine interne et oncologie - Hôpital Inter Armées de Begin
      • Saint Nazaire, France, 44600
        • Service d'Oncologie Médicale - Clinique Mutualiste de l'Estuaire, Cité Sanitaire
      • Saint-Grégoire, France, 35760
        • Service d'Oncologie Radiothérapie - Centre Hospitalier Privé de Saint-Grégoire
      • Senlis, France, 60309
        • Service d'Oncologie Médicale - Groupe Hospitalier Public du Sud de l'Oise - Site de Senlis
      • Sens, France, 89108
        • Service d'Oncologie Médicale - Centre Hospitalier de Sens
      • Strasbourg, France, 67065
        • Service d'Oncologie Médicale - Centre Paul Strauss
      • Thonon les Bains, France, 74203
        • Service de Chirurgie et Oncologie Gynécologique et Mammaire - Hôpitaux du Léman
      • Toulouse, France, 31300
        • Service d'Oncologie Médicale - Institut Claudius Regaud
      • Vandoeuvre lès Nancy, France, 54519
        • Service d'Oncologie Médicale - Institut de Cancérologie de Lorraine
      • Villejuif, France, 94800
        • Service de Médecine Oncologique - Institut de Cancérologie Gustave Roussy
  • Italy
      • Aviano, Italy
        • Centro di Riferimento Oncologico - CRO,IRCCS
      • Legnago, Italy
        • Azienda Ulss 21 Legnago
      • Milano, Italy
        • Fondazione IRCCS Istituto Nazionale Tumori
      • Mirano, Italy
        • Ulls13 - Mirano
      • Sassuolo, Italy
        • Ospedale Nuovo di Sassuolo
      • Torino, Italy
        • Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo
  • Sweden
      • Linköping, Sweden
        • Linkoping University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

68 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A:Paclitaxel + Carboplatin every 3 weeks
Patients randomized to the arm A receive 6 courses the following regimen: Paclitaxel 175 mg/m²/3 hours, I.V. and carboplatin AUC 5, I.V. every 3 weeks (1 cycle = 21 days).
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.
Experimental: B:Carboplatin monotherapy every 3 weeks
Patients randomized to the arm B receive 6 courses the following regimen: Carboplatin monotherapy AUC 5 or 6 every 3 weeks (1 cycle = 21 days).
Drug: 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.
Experimental: C:Weekly Paclitaxel and Carboplatin
Patients randomized to the arm C receive 6 courses the following regimen: weekly paclitaxel 60 mg/m²/1 hour and weekly carboplatin AUC 2 (d1, d8, d15 ; d1=d29) (1 cycle = 28 days).
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment success.Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity
Time Frame: After 6 courses of chemotherapy i.e 4.5 to 6 months (depending on the arm)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapeutical strategy
Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
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)
Overall Survival
Time Frame: 2.5 years
Overall survival is defined as the time period from the date of randomization to the date of death.
2.5 years
Progression-free survival
Time Frame: 2.5 years
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
Quality of Life
Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
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)
Safety and tolerability
Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
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)
Aging biomarkers
Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)
Aging biomarkers are represented by the expression level of cathelin-related antimicrobial peptide or CRAMP, stathmin, EF-1α, and chitinase
At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Claire FALANDRY, MD, Service d'oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2013

Primary Completion (Actual)

February 1, 2020

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

November 22, 2013

First Submitted That Met QC Criteria

November 27, 2013

First Posted (Estimate)

December 4, 2013

Study Record Updates

Last Update Posted (Actual)

August 4, 2020

Last Update Submitted That Met QC Criteria

August 3, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-772

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ovarian Cancer

Clinical Trials on Paclitaxel + Carboplatin every 3 weeks

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Philippines

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe