platinum-sensitive and platinum-resistant relapsed ovarian cancer
Conditions
Sponsors
UZLeuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of informed consent prior to any study specific procedures 2.Patients with recurrent epithelial carcinoma of the ovary, fallopian tube or primary peritoneum with following histology (rationale for inclusion beyond high-grade serous: see Pennington et al. 2014): ? Serous (high grade = grade 2 or 3) ? Endometrioid (all grades) ? Clear-cell (all grades) ? Carcinosarcoma ? Undifferentiated carcinoma 3.Female patients (= 18 years) with platinum sensitive relapsed ovarian cancer (PSOC), excluding known deleterious germline or somatic BRCA1/2 mutations, OR Platinum resistant relapsed ovarian cancer (PROC), including cases with known deleterious BRCA1/2 germline or somatic mutations. 4.At least 1 previous line of chemotherapy 5.Patients must have measurable disease on imaging according to RECIST criteria 1.1 6.Archival tissue of the primary tumor available (either fresh-frozen or FFPE) 7.Patients consent for a biopsy of the relapsed tumor at the start of treatment and at disease progression. A failure to obtain these samples (due to technical or safety reasons) does however not exclude patients from the study. 8.Patient consent to germline BRCA1/2 testing. 9.Patients have a normal organ and bone marrow function measured within 28 days of randomization, as defined below: a.Hemoglobin = 10.0 g/dL with no blood transfusions in the past 28 days b.Absolute neutrophil count (ANC) = 1.5 x 109/L c.Platelet count = 100 x 109/L d.Total bilirubin = 1.5 x institutional upper limit of normal e.Aspartate aminotransferase (AST) (SGOT) / Alanine aminotransferase (ALT) (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be = 5x ULN f.Serum creatinine = 1.5 x institutional upper limit of normal (ULN) 10.Previous treatment with a PARP-inhibitor is allowed. 11.Eastern Cooperative Oncology Group (ECOG) performance status 0-2 12.Patients must have a life expectancy = 16 weeks 13.Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 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 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1.Involvement in the planning and/or conduct of the study 2.Previous randomisation in the present study 3.Patients with primary platinum-refractory disease (i.e. platinum refractory during or after first line of chemotherapy). 4.Patients with a known hypersensitivity to olaparib or any of the excipients of the product 5.Patients with a known hypersensitivity to comparator agent 6.Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome 7.Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to olaparib treatment. Target lesion should be outside radiated field. 8.Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir 9.Patients with myelodysplastic syndrome/acute myeloid leukaemia 10.Immunocompromised patients (e.g. HIV) requiring treatment or active Hepatitis B or C 11.Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days 12.Major surgery within 2 weeks of starting study treatment. Furthermore, patients must have recovered from any effects of any major surgery. 13.Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent 14.Patients with uncontrolled seizures. 15.Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for = 3 years 16.Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication 17.Pregnant or breast feeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstrate the value of a ctDNA-based assay for homologous recombination deficiency to predict response to olaparib monotherapy. This analysis will also be performed according to platinum-sensitivity (platinum-sensitive versus platinum-resistant).;Secondary Objective: -Demonstrate the value of a ctDNA-based assay for homologous recombination deficiency to predict duration of response, disease control rate, progression-free survival and overall survival to olaparib monotherapy. These analyses will also be performed according to platinum-sensitivity (platinum-sensitive versus platinum-resistant). -Demonstrate the value of a tissue DNA-based assay (fresh frozen/FFPE) for homologous recombination deficiency to predict response, progression-free survival, duration of response and overall survival to olaparib monotherapy. -Assess the efficacy of olaparib monotherapy versus phycician’s choice chemotherapy after randomization in the study with regards to response, duration of response, progression-free survival and overall survival in patients with both a platinum-sensitive and a platinum-resistant relapse. The study is powered for subgroup analyses on these 2 cohorts. -Assessment of Quality of Life for all enrolled subjects ;Primary end point(s): OOR (overall objective response) by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary ctDNA-based genomic classifier;Timepoint(s) of evaluation of this end point: Q3 2018 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -DOR (duration of response) by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary ctDNA-based genomic classifier -DCR (disease control rate) at 12 weeks and later by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary ctDNA-based genomic classifier -PFS (progression-free survival) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary ctDNA-based genomic classifier -OS (overall survival) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary ctDNA-based genomic classifier -OOR (overall objective response) by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary tissue DNA-based genomic classifier -DOR (duration of response) by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary tissue DNA-based genomic classifier -DCR (disease control rate) at 12 weeks and later by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary tissue DNA-based genomic classifier -PFS (progression-free survival) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary tissue DNA-based genomic classifier -OS (overall survival) in patients receiving olaparib monotherapy, stratified for HR-deficiency as defined by a binary tissue DNA-based genomic classifier -OOR (overall objective response) by modified RECIST v1.1 (Eisenhauer et al. 2009) in patients receiving olaparib monotherapy vs physician’s choice chemotherapy after randomization in the study -DOR (overall objective response) by modified R | — |
Countries
Belgium
Contacts
Public ContactJoke De Roover
UZLeuven
Outcome results
None listed