1. Elderly Women Ovarian Cancer Multicenter, randomized trial of carboplatin +/- paclitaxel in vulnerable elderly patients with stage III-IV advanced ovarian cancer 1 Participating Groups GINECO, AGO, MITO, ANZGOG, Canada, JGOG, GOTIC, NSGO

2.  In the population of vulnerable patients : Which is the best treatment regimen based on their respective benefit/risk ratio ?  Population of interest : Vulnerable patients defined with GVS ≥ 3  Randomized phase II trial  Main endpoint : Treatment completion rate with an interim analysis on efficacy and safety profiles (Bryant and Day method) 2

3. 3 *GVS = Geriatric Vunerability Score : - score ADL < 6 - score IADL < 25 - score HADS > 14 - albuminemia < 35g/L - Lymphopenia < 1G/L GVS =  factors with vulnerable score

4. 4 Based upon :  Initial debulking surgery versus planned interval debulking surgery  No macroscopic residue versus macroscopic residue (including surgery not done)  Interval debulking intent  Cancer stage (stage III versus stage IV)  Country

5. 5

6. 6 To compare the rate of success to deliver 6 courses of chemotherapy without progression at 6 months or unacceptable toxicity* of 3 different regimens in vulnerable elderly patients Screening Chemotherapy 6 cycles 6 month visit GVS>3 * Unacceptable Toxicity = is defined as a major adverse event related to chemotherapy or treatment procedures leading either to early treatment stopping, to an unplanned hospital admission or to death. Imagery QOL Imagery QOL Follow-up every 3 mo. (up to 2 years) Follow-up every 3 mo. (up to 2 years) +/- Interval debulking (stratified)

7. 7  The first step will include 22 patients in each arm (total = 66 patients for the 3 arms);  An interim analysis will be conducted when 22 patients in each arm will have completed their 6 courses of chemotherapy: - if a chemotherapy regimen is associated with more than 8/22 treatment failure, the regimen will be considered as having insufficient activity (expected number of failure n= 3) and the regimen will be dropped for the second step of the study; - if a chemotherapy regimen is associated with more than 6/22 major adverse event leading either to early treatment stopping, or to hospitalization for toxicity or to death, the regimen will be considered as having too high toxicity (expected number of major adverse event n= 3) and the regimen will be dropped for the second step of the study;  The second step of the study will be run with the chemotherapy regimens considered as active enough and tolerable at the interim analysis. This step will include an additional 58 patients per arm with the following assumptions: - a risk of accepting a regimen having insufficient activity α1 = 0,05, - a risk of accepting a regimen with too high toxicity α2 = 0,05, - a risk of rejecting regimen active enough (1-β) = 0,1 - with an unacceptable rate of disease progression at 6 month of > 0,4 - and an unacceptable toxicity rate > 0,3.  The total number of patients per arm will be of 80 for a maximum total number of patients of 240 if all 3 regimens are selected for step 2.  After completion of the 6 chemotherapy cycles, conditions to reject the experimental arms are the following: number of patients with insufficient efficacy n> 26/80 and/or number of patients with unacceptable toxicity n> 18/80 (expected tumour progression or treatment failure: 9, major adverse events: 9).

8. 8  Woman >70 years old  Histologically or cytologically proven FIGO stage III to IV epithelial ovarian cancer or peritoneal primary and 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. GVS is the sum of geriatric covariates scores found to predict poor survival : ADL score 14, albuminemia <35g/L and lymphopenia <1G/L.  Neutrophils ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L and hemoglobin ≥9 g/dL  No icterus.

9. 9  Prior history of cancer,excepted in situ cancer of the cervix, in situ urothelial cancer, cured basocellular cancer and any other cancer treated and in complete remission for more than 2 years.  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) of the laboratory, SGOT-SGPT >3 fold UNL.

10. 10

11. 11  Arcagy – Gineco trial;  Sponsor: LES HOSPICES CIVILS DE LYON (HCL);  Italian coordinating center: NCI of Milan;  Planned Italian study start: January 2015;  NCI of Milan financial support for insurance  Conference call for site initiation visit

12. SitePrincipal Investigator IRCCS Istituto Nazionale Tumori – Milano CENTRO COORDINATORE (approved on 27/05/2014) Domenica Lorusso IRCCS Istituto Nazionale Tumori Fondazione Pascale - Napoli Sandro Pignata Policlinico Universitario A. Gemelli - RomaGiovanni Scambia A.O.Universitaria Policlinico di BariMarco Marinaccio Ospedale Fatebenefratelli - RomaEnrico Breda Azienda Ospedaliera per l'Emergenza Cannizzaro di Catania Paolo Scollo IRCCS Istituto Regina Elena (IFO) – RomaAntonella Savarese IRCCS Azienda Ospedaliera S. Maria Nuova – Reggio Emilia Corrado Boni IRCCS Centro di Riferimento Oncologico (CRO) - AvianoRoberto Sorio IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Meldola Ugo De Giorgi A.O.Universitaria Federico II - NapoliRossella Lauria Presidio Ospedaliero di FaenzaStefano Tamberi 12 To activate new sites please contact: domenica.lorusso@istitutotumori.mi.it domenica.lorusso@istitutotumori.mi.it Elisa.grassi@istitutotumori.mi.it