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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT02001272

Collaborator

(none)

120

Enrollment

Locations

Arms

Actual Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Paclitaxel + Carboplatin every 3 weeks Drug: Carboplatin monotherapy every 3 weeks Drug: Weekly Paclitaxel and Carboplatin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Feb 1, 2020

Actual Study Completion Date :

Feb 1, 2020

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Treatment success.Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity [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.

Secondary Outcome Measures

Therapeutical strategy [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.
Overall Survival [2.5 years]
Overall survival is defined as the time period from the date of randomization to the date of death.
Progression-free survival [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.
Quality of Life [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
Safety and tolerability [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
Aging biomarkers [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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