Download Recurrent ovarian, primary peritoneal or fallopian tube

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
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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.
RATIONALE AND BACKGROUND
RATIONALE AND BACKGROUND
DETERMINAZIONE DELL'AGENZIA ITALIANA
DEL FARMACO, 9 DICEMBRE 2008
(Gazzetta Ufficiale n. 1 del 02.01.09, Supplemento ordinario n. 1)
Platinum resistant/refractory
>3 lines CT
Physician’s
choice
Recurrent ovarian,
primary peritoneal or
fallopian tube cancers
Random
1:1
Letrozole, Oral
2.5 mg daily
Primary:
STUDY OBJECTIVES
DCR= 12-week disease control rate (DCR; CR, PR or SD;
according to RECIST v1.1)
Secondary:
•Quality of life using the QLQ-C30 and QLQ-0V28, FOSI (every 3
/4 weeks)
•TSST
•PFS
•OS
•Radiological response rate (in patients with measurable disease)
•Duration of response
•CA-125 response rate per GCIG
•Toxicity profile
•Biomarker analysis (ER status)
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
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
STATISTICS PROTOCOL
Phase II randomized
PICK-THE-WINNER
The sample size in this trial was decided to be either 40 or 100
patients depending on the results of the interim efficacy analysis.
•DCR at week 12 for patients treated with an investigator choice of
chemotherapy was assumed to be 30%. The number of patients in the
trial would be chosen to give a probability of 67% of correctly picking the
letrozole treatment arm as the winner if the DCR for the letrozole arm was
35%.
•2-step trial design allowed for an early safety analysis after random
assignment of 40 patients (20 per arm) and treatment of at least 12 weeks
and after radiological assessment.
The trial will continue continue if either > 1 of the first 12 patients with at
least one measurable lesion included in the letrozole arm had a complete
response (CR) or PR at weeks 6 or 12, or if > 5 of the first 20 patients
included in the letrozole arm showed a CR, PR, or stable disease (SD) at
week 12.
•All treated patients who received at least one cycle of letrozole or
chemotherapy will be included in the safety and efficacy analyses.
ADMINISTRATIVE INFORMATION
•Academic trial
• Sapienza University of Roma sponsor
•Data center: Sapienza of Roma (MITO center)
•Planned study start: April 2017
•Epionpharma support: financial support for insurance,
IHC and data management.
MITO - 23