platinum-resistant ovarian carcinoma or Fallopian tubes or primary of peritoneum MedDRA version: 21.1 Level: LLT Classification code 10033131 Term: Ovarian carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: YONDELIS - 1 MG POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) 1 FLACONCINO
Product Name: yondelis
Product Code: [ET-743]
Pharmaceutical Form: Po
Sponsors
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA IRCCS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years. 2. Provision of written informed consent prior to any study specific procedures. 3. Patients willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations. 4. Patients with histologically proven high-grade serous or endometrioid ovarian/fallopian tube/primary peritoneal cancer 5. Patients who have received at least one platinum based regimen and relapsing after a maximum of two previous lines of chemotherapy. Any immunotherapy administered will not be considered as a prior line of therapy. Use of biological agents, such as bevacizumab, in combination with previous lines of chemotherapy will be allowed. 6. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for histological revision in one of the participating centers prior to enrolment. After enrolment, FFPE must be shipped to Coordinating Center for ancillary studies, under subscription of the specific biomarker ICF. 7. One or two previous lines of chemotherapy (to be eligible patient should have received at least one line of platinum-based chemotherapy) 8. Measurable disease according to RECIST v1.1. Baseline evaluations must be completed within 28 days prior to enrollment with computed tomography (CT) or magnetic resonance imaging (MRI). 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0/1. 10. Estimated life expectancy = 16 weeks. 11. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1 Postmenopausal is defined as: - Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments or chemotherapy; - LH and FSH levels in the post menopausal range for women under 55; - Amenorrheic for 1 year for women = 55; - Radiation-induced oophorectomy with last menses >1 year ago; - Surgical sterilisation (bilateral oophorectomy or hysterectomy). 12. Left Ventricular Ejection Fraction = 50% and/or above lower institutional limit of normality 13. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of treatment: • Hemoglobin > 10.0 g/dl with no blood transfusion in the past 28 days • Absolute neutrophil count (ANC) >1,500/mm3 • Platelet count ¿ 150,000/µl • Total bilirubin 2.5 x ULN, consider hepatic isoenzymes 5-nucleotidase or gamma glutamyl transpeptidase (GGT) to rule out bone origin). • PT-INR/PTT =65 years) yes F
Exclusion criteria
Exclusion criteria: 2. Previous enrolment in the present study. 3. Participation in another clinical study with an investigational product during the last 4 weeks. 4. More than two previous lines of chemotherapy (NOTE: Any immunotherapy administered will not be considered as a prior line of therapy). Use of biological agents, such as bevacizumab, in combination with previous lines of chemotherapy will be allowed. 6. Dementia or significantly altered mental status that would prevent the understanding or rendering of informed consent and compliance with the requirements of this protocol. 7. Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. In particular for history of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent. 8. Immunocompromised patients, 9. Active clinically serious infections (> grade 2 NCI-CTC version 4.03). 10. Active viral hepatitis (HBV or HCV infection) 11. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, does not require corticosteroid treatment, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry). A scan to confirm the absence of brain metastases is not required. 12. Patients with seizure disorders requiring medication (such as steroids or anti-epileptics). 13. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed during the screening phase and on day 1 of the first cycle before the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 5 months after last dose of study drug. 14. Patients with evidence or history of bleeding diathesis. 15. Patients unable to swallow orally administered medication 16. Uncontrolled diabetes (fasting glucose > 2 x ULN). 17. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent 19. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. 20. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). 21. Major surgery within 4 weeks of start of study and patients must have recovered from any effects of any major surgery. 22. Investigational drug therapy outside of this trial during or within 4 weeks of study entry. 23. Prior exposure to the study drugs or their analogues. 24. Patients with known hypersensitivity to trabectedin, olaparib or to their excipients. 25. Patients can receive a stable dose of bisphosphonates for bone metastases before and during the study as long as these were started at least 4 weeks prior to treatment with the study drugs. 26. Substance abuse, medical, ps
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary (cohort A) Primary objective of the study will be to assess the antitumor activity of Trabectedin + Olaparib combination as second- or third-line treatment of relapsed and high-grade serous or endometrioid ovarian cancer evaluated by means of progression-free survival rate at 4 months and/or objective response rate according to RECIST1.1. Primary (cohort B) Primary objective of the study will be to assess the antitumor activity of Trabectedin and olaparib combination as second- or third-line treatment of relapsed and high grade serous or endometrioid ovarian cancer evaluated by means of progression-free survival rate at 4 months (according to RECIST1.1).;Secondary Objective: Secondary (cohort A) Secondary objectives of the study will be to explore the activity of Trabectedin + Olaparib in this unfavorable subset of serous or endometriod OC. This will be accomplished by both recording overall survival, progression-free survival, duration of response, RECIST response rate (dimensional reduction), clinical benefit rate (defining as a success any patient non-progressing at three-months), CA-125 response rate, assessments of Quality of Life (QoL), and safety. Finally, a specific effort will be conducted to study details of the biology of tumors showing benefit from the combination. Secondary (cohort B) Secondary objectives of the study will be to explore the activity of T+O in this unfavorable subset of serous or endometrioid OC. This will be accomplished by both recording overall survival, progression-free survival, duration of response, RECIST 1.1 response rate (dimensional reduction), clinical benefit (defining as a success any patient non-progressing at t;Primary end point(s): Progression-free survival rate at 4 months (PFS);Timepoint(s) of evaluation of this end point: 4 montsh from first dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival (PFS).; overal survival;Timepoint(s) of evaluation of this end point: at disease progressione; at patient death | — |
Countries
Italy
Contacts
Public ContactONCOLOGIA MEDICA
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA
Outcome results
None listed