Circulating tumor DNA guiding (Olaparib) Lynparza® treatment in Ovarian Cancer (CLIO). Establishing the value of a ctDNA-based HRD assay for predicting olaparib response in women with relapsed ovarian cancer

Phase 1

• Conditions: platinum-sensitive and platinum-resistant relapsed ovarian cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-005838-22-BE
• Lead Sponsor: ZLeuven

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-06-10
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 160

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

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

Study & Design

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