1. MITO 26
PHASE II TRIAL ON TRABECTEDIN IN THE TREATMENT OF ADVANCED UTERINE AND OVARIAN CARCINOSARCOMA (CS)

2. Study design Study Drug
This is a Phase II, multi-centre, single arm study aiming at evaluating efficacy and toxicity of Trabectedin in a population of advanced or recurrent uterine and ovarian carcinosarcoma.
A central revision of slides is required. Dr Paolini (National Cancer Institute of Milan) and Dr Losito (National Cancer Institute of Naples) will provide the revision. For any patient 4 x 10 μm unstained slides and 5x 4μm stained H&E slides must be provided .
Study Drug
Trabectedin 1.3 mg/mq iv (central line) d1 q 21 until progression of disease, unacceptable toxicity or patient’s consent withdrawal
MITO 26

3. Objectives
Primary:
To determine the activity in terms of objective response rate by RECIST
version 1.1 (Complete and Partial Response [CR + PR]) with trabectedin in
patients with advanced uterine and ovarian carcinosarcoma
Secondary:
Progression free survival;
Overall survival;
Duration of response;
Toxicity.
MITO 26

4. Inclusion Criteria
Histologically documented Stage I-IV or recurrent uterine or ovarian
carcinosarcoma not amenable to surgery or radiotherapy;
No more than 2 previous chemotherapy lines;
PS 0-2 (ECOG);
Age> 18;
Measurable disease;
Life expectancy of at least 3 months;
Adequate organ functions;
Previous Radiotherapy treatment for uterine carcinosarcoma is allowed;
No other invasive malignancy within the past 3 years except non-melanoma skin
cancer;
Written Informed Consent.
MITO 26

5. Exclusion Criteria More than 2 previous chemotherapy lines;
More than 2 previous chemotherapy lines;
Single tumor lesion inside a previous irradiated filed;
Pregnant (potentially fertile patients must be not in pregnancy during and for at
least 3 months after study participation and must have a negative serum
pregnancy test);
Active infection requiring antibiotics;
Symptomatic peripheral neuropathy > grade 2 according to the NCI Common
Toxicity Criteria;
Congestive heart failure or angina pectoris even if it is medically controlled.
Previous history of myocardial infarction within 1 year from study entry,
uncontrolled high risk hypertension or arrhythmia;
Unstable or severe intercurrent medical condition that, in the opinion of the
investigator, might interfere with achievement of study objectives;
Psychological or sociological conditions, addictive disorders, or family problems,
which would preclude compliance with the protocol.
MITO 26

6. Statistical consideration
The study is planned according to Simon’s Optimal two-stage design.
The primary endpoint of this study is to evaluate the activity of trabectedin in terms of the objective response rate (ORR) in patients with advanced uterine and ovarian carcinosarcoma. By considering the expected activity of the new regiment in this disease, the 25% benchmark rate will be adopted as H1 hypothesis, while a 10% rate of H0 hypothesis will be taken as comparator.
In stage 1, 18 evaluable patients will be accrued. If 3 patient at least will be responding, enrolment will be extended to the 2nd stage for further 25 patients.
If, out of the total of 43 patients, 8 at least will be responding, treatment will be declared worthy for further investigations.
MITO 26

7. Administrative Information
Academic trial
NCI of Milan sponsor
Data center: NCI of Milan (MITO center)
Planned study start: March 2017
Pharmamar: drug supply
Insurance provided by Coordinator center
Enrolled patients: 8/18 (43 pts overall)
Acrivated sites: 6/17
To participate please contact:
MITO 26