overall survival of patients with recurrent ovarian, primary peritoneal or fallopian tube cancers of BRCA mutated or BRCAness phenotype treated with trabectedin compared to a standard treatment

Phase 1

• Conditions: recurrent ovarian, primary peritoneal or fallopian tube cancers of BRCA mutated or BRCAness phenotype patients; MedDRA version: 20.0Level: LLTClassification code 10006888Term: Ca ovarySystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004472-30-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-21
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 244

Inclusion Criteria

1. Female of age 18 years or older
2. Histologicallyorcytologically documentedinvasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer
3. Platinum resistant or sensitive patients with either:
a. BRCA mutated patients
b. BRCAness phenotype: patients who have received and responded (subsequent PFI>6 months) to at least 2 previous platinum based chemotherapy lines
c. Platinum sensitive patients who are not able to receive or not willing to receive other platinum treatments
4. Measurable and evaluable disease per RECIST 1.1(Subjects with isolated rising CA-125 without radiologically visible disease areexcluded)
5. ECOG performance status 0 or 1
6. No limitsinthenumber of previous chemotherapy lines,previous treatment with parp inhibitors is allowed
7.Left Ventricular Ejection Fraction (LVEF) =institutional lower limit normal
8. Life expectancy of at least 3 months
9.Adequate organ functions:
a. Hematopoietic; Absolute neutrophil count = 1,500/mm3
b. Platelet count = 100,000/mm3; Hemoglobin = 9 g/dl
c. Hepatic; AST and ALT = 1.5 times upper limit of normal (ULN)* ; Alkaline Phosphatase = 2.5 times ULN*; Bilirubin= 1.5 times ULN NOTE: * = 3 times ULN if liver metastases are present
d. Renal; Creatinine Clearance = 45 ml/min or Serum Creatinine =1.5 x ULN
e. Serum Albumin >2.5 g/dl
10. No other invasive malignancy within the past 3 years except non-melanoma skin cancer or in situ cervical cancer (patients with previouscancersmay be enrolled providing that no recurrenceshave be reported in the last 3 years)
11. Written Informed Consent
12. Adequately recovered from the acute toxicity of any prior treatment
13.For agents in the standard arm, also refer to the local prescribing information with regards to warnings, precautions, and contraindications
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

Exclusion Criteria

1. Prior exposure to trabectedin
2. Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone
3. Subjects with borderline ovarian cancer, ie. Subject with low malignant potential tumors are excluded
4. Less than 2 reported responses to platinum (i.e. subsequent recurrences at least 6 months after the first and the second platinum based
treatment), unless BRCA mutation is documented.
5. Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy
6. History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3
years or longer
7. Known clinically relevant CNS metastases, unless treated and asymptomatic
8. Other serious illnesses, such as:
a.Congestiveheartfailureorangina pectoris,myocardialinfarction within 1 year before enrolment; uncontrolled arterial hypertension or arrhythmias.
b.Psychiatric disorder that prevents compliance with protocol.
c.Active viral hepatitis; or chronic liver disease.
d.Active infection.
e. Any other unstable medical conditions.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to compare the treatment groups in terms of overall survival (OS);Primary end point(s): The primary objective is to compare the treatment groups in terms of overall survival (OS)<br>;Timepoint(s) of evaluation of this end point: OS will be measured from the date of randomization to death due to any cause<br>;Secondary Objective: The secondary objectives are to compare the treatment groups in terms of:<br>• Progression free survival (PFS) In case of CA 125 progression according to GCIG criteria is documented, a confirmatory CT scan and a radiological CT progression will be required.<br>•Radiological response rate (in patients with measurable disease)<br>•Duration of response<br>•CA-125 response rate per GCIG and change in CA-125<br>•Toxicity profile<br>•Quality of Life assessments using QLQ-C30 and QLQ-OV28<br>questionnaires.<br>