1. Claudia Marchetti Pierluigi Benedetti Panici
Randomized phase II randomized trial on Letrozole vs clinician’s choice chemotherapy in heavily pretreated recurrent ovarian, primary peritoneal or fallopian tube cancers
MITO – XX
Claudia Marchetti Pierluigi Benedetti Panici

2. `
A maximum of three lines of subsequent relapse treatment seems to be beneficial for patients with recurrent ovarian cancer.
Optimal primary tumor debulking and platinum sensitivity remain independent prognostic factors even after more frequent relapses.

3. RATIONALE AND BACKGROUND

4. Abs 5515, ASCO 2017

5. RATIONALE AND BACKGROUND
DETERMINAZIONE DELL'AGENZIA ITALIANA DEL FARMACO, 9 DICEMBRE 2008
(Gazzetta Ufficiale n. 1 del , Supplemento ordinario n. 1)

6. Recurrent ovarian, primary peritoneal or fallopian tube cancers
Platinum resistant/refractory
>3 lines CT
Physician’s choice
Random1:1
Recurrent ovarian, primary peritoneal or fallopian tube cancers
Letrozole, Oral 2.5 mg daily
paclitaxel
PLD
Topotecan
gemcitabine 6

7. STUDY OBJECTIVES Proportion of patients alive at 12 months QoL (HRQoL)
Primary:
Proportion of patients alive at 12 months
SECONDARY ENDPOINTS:
QoL (HRQoL) OS RR
PFS
TPST
TSST
Biomarker analysis (ER status)
PROs were assessed with three instruments: European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30),5 EORTC QLQ Ovarian Cancer Module 28 (OV28),6 and the eight-item Functional Assessment of Cancer Therapy–Ovarian Cancer Symptom Index (FOSI). 7

8. INCLUSION CRITERIA Female of age 18 years or older
Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or
fallopian tube cancer
Platinum resistant or refractory
>3 previous chemotherapy lines
primary tumor specimen available for measurement of biochemical markers
ECOG performance status 0 -2
Measurable and evaluable disease per RECIST 1.1(Subjects with isolated rising CA-125 without radiologically
visible disease are excluded)
Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit normal
Adequate organ functions 8

9. EXCLUSION CRITERIA
Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone
Subjects with borderline ovarian cancer, ie. Subject with low malignant potential tumors are excluded
Less than 3 lines of previous therapy
Platinum sensitive diseaseor refractory
primary tumor specimen unavailable for measurement of biochemical markers
Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy
History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer
Severe osteoporosis 9

10. CAMBIARE END POINT E FARLO DIVENTARE PFS
STATISTICS PROTOCOL
Phase II randomized
With 150 patients, the study will have 80% power to detect an increase in the proportion of patients alive at 12 months from 48 % in the control arm to 65% in the experimental arm with a two-tailed alpha error of 0.2.
CAMBIARE END POINT E FARLO DIVENTARE PFS
Considerando il setting clinico mi chiedo se non abbia
piu' senso passare PFS e QoL come end points co-primari
(con calcolo del sample size calcolato su PFS; si puo' poi
calcolare sulla base del campione previsto l'entita' della differenza
nell'outcome di QoL con errori alpha e beta relativi) e passare
OS as secondary end-point). 10

11. OTHER SUGGESTIONS
Inserire valutazioni QoL protoocllo ANZ GOG tra i criteri di stratificazione (lavoro pubblicato GCIG)
PER LA QOL UTILE ANCHE IL FOSI
Aggiungerei adl iadl per la valutazione qualità di vita
SAREBBE INTERESSANTE POTER AVERE IL DATO DEI Recettori Ormonali INCORAGGIANDO UNA AGOBIOPSIA DELLA RECIDIVA
patient’s ability to perform
activities of daily life (ADL) and instrumental activities
of daily life (IADL). 11

12. ADMINISTRATIVE INFORMATION
Academic trial
Sapienza University of Roma sponsor
Data center: Sapienza of Roma (MITO center)
Planned study start: Dec 2017 (max)
Epionpharma support: financial support for insurance, IHC and data management.
MITO - 23 12

14. Study N
N of Prior reatemtns
Median PF(
Papadimitriou et al, 2004 27
1- 2 (78% of cohort) Q3 (22%)
2.5 for all-comers/17.6 for responders
Smyth et al, 2007 42
1- 2 (75%) 92 (23%)
>6 in 26% cohort
Ramirez et al, 2008 33
>3 (74%)
2.1 [partial response/stable disease]
Stasenko et al, 2014 10
4- 6 (26%)
8.5 (letrozole)