1. Fondazione IRCCS Istituto Nazionale Tumori
TEMOZOLOMIDE TRIAL
Phase II study on Temozolomide in MGMT promoter methylated recurrent ovarian cancers
Principal investigators
Filippo de Braud
Francesco Raspagliesi
Sub Investigator
Domenica Lorusso
Fondazione IRCCS Istituto Nazionale Tumori

2. Rational
TEMOZOLOMIDE

3. Rational
TEMOZOLOMIDE

4. Study design
This is an open-label, prospective, Phase II trial evaluating the activity and safety of temozolomide treatment in recurrent clear cell and mucinous ovarian cancer patients selected for MGMT promoter methylation.
Administration of Clinical Trial Medication
temozolomide will be given at the dose of 200 mg/m2 for 5 days every 28 days per os until disease progression or unacceptable toxicity or patient’s refusal.
TEMOZOLOMIDE

5. Objectives
Primary:
To evaluate the activity (in terms of objective response rate by RECIST version 1.1) of temozolomide treatment in recurrent clear cell and mucinous ovarian cancer patients selected for MGMT promoter methylation.
TEMOZOLOMIDE

6. Objectives Secondary: To assess: Duration of response;
Progression-free survival [the diagnosis of progression will be
assessed by radiological criteria; CA 125 increases alone (GCIG
criteria of progression) will not be considered as progression of
disease without a radiological confirmation of progression;
Overall Survival (OS)
Safety profile of temozolomide in this patient population.
TEMOZOLOMIDE

7. Inclusion Criteria
Recurrent clear cell and mucinous ovarian cancer patients with MGMT promoter methylation (evaluated by immunoistochemistry) for which no active treatments have been available;
At least one previous platinum-pacltaxel chemotherapy line, no limitation in the number of previous chemotherapy lines;
Patient´s written informed consent before any clinical trial-specific procedure;
18 years-of-age or older;
Measurable disease as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines;
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1;
Adequate bone marrow function;
Adequate renal and hepatic function;
Albumin ≥ 25 g/l;
Adequately recovered from the acute toxicity of any prior treatment.
TEMOZOLOMIDE

8. Exclusion Criteria Prior exposure to temozolomide;
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;
Other serious illnesses, such as:
Congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrollment; uncontrolled arterial hypertension or arrhythmias;
Psychiatric disorder that prevents compliance with protocol;
Active viral hepatitis; or chronic liver disease;
Active infection;
Any other unstable medical conditions
TEMOZOLOMIDE

9. Statistical consideration
Sample size
Expected response rate to conventional chemotherapy in recurrent clear cell or mucinous ovarian cancer is in median 5%. We plan to enroll 21 patients in this prospective phase II study (alfa error 0.05, beta 80%) to demonstrate a 20% response rate in MGMT methylated clear cell of mucinous carcinoma treated with temozolomide. Assuming a 10% drop out and/or not evaluable patients, a total of 25 patients will be enrolled in 18 months.
Efficacy evaluation
Disease evaluation will be assessed at baseline and every 3 cycles by CT-scan or RMI. The same exam performed at baseline will be repeated at each evaluation. Disease response will be evaluated according to Recist version 1.1 criteria.
TEMOZOLOMIDE

10. Administrative Information
Academic trial
NCI of Milan sponsor
Data center: NCI of Milan (MITO center)
Planned study start : April 2017
Temozolomide will be provided by the company free of charge and shipped
from the Coordinator Center
MGMT methylation will be evaluated at NCI of Rome
Insurance provided by the Coordinator Center
To participate please contact:
TEMOZOLOMIDE

11. TEMOZOLAMIDE STUDY Numero Centro Nome centro Città PI 1
Fondazione IRCCS Istituto Nazionale Tumori
Milano
Francesco raspagliesi 2
P.O. "A.Perrino" ASL Brindisi
Brindisi
Saverio Cinieri 3
Policlinico di Modena
Modena
Roberto Sabbatini 4
Ospedale degli Infermi
Faenza
Stefano Tamberi 5
Ospedale Umberto I
Lugo