combination of trabectedin and olaparib in ovarian cancer, fallopian tubes and primary of peritoneum already resistant to standard platinum drugs

Phase 1

• Conditions: platinum-resistant ovarian carcinoma or Fallopian tubes or primary of peritoneum; MedDRA version: 21.1Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

• Registration Number: EUCTR2018-000230-35-IT
• Lead Sponsor: FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA IRCCS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 10 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 66

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 < upper limit of normal (ULN)
•Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) = 2.5 x ULN
•Alkaline phosphatase < 2.5 x ULN (in case alkaline phosphatase >2.5 x ULN, consider hepatic isoenzymes 5-nucleotidase or gamma glutamyl transpeptidase (GGT) to rule out bone origin).
•PT-INR/PTT < 1.5 x ULN (Patients who are being therapeutically anticoagulated with an agent such as warfarin, direct oral anticoagulation agents (DOACs) or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists. Patients treated with warfarin or DOACs must be shifted to low molecular weight heparin/fondaparinux)
•Serum creatinine < 1.5 x ULN or creatinine clearance = 60 ml/min
•Albumin = 25 g/l
•Creatine phosphokinase (CPK) = 2.5 x ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 46
F.1.3 Elderly (>=65 years) yes
F

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

Study & Design

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