Overview

Resistant Ovarian Cancer, Olaparib and Liposomal Doxorubicin

Status:
Active, not recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
Female
Summary
Impact of the combination of Olaparib and Pegylated Liposomal Doxorubicin on improvement of progression-free survival at 6 months in patients with platinum resistant advanced ovarian cancer.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Grupo Español de Investigación en Cáncer de Ovario
Collaborator:
AstraZeneca
Treatments:
Doxorubicin
Liposomal doxorubicin
Olaparib
Criteria
Inclusion Criteria:

- Provision of informed consent prior to any study specific procedures. Procedures
conducted as part of the subject's routine clinical management (e.g., blood count,
imaging study) and those obtained prior to signing of informed consent may be utilized
for screening or for baseline purposes provided these procedures are conducted as
specified in the protocol.

- Patients with histological or cytological confirmed high grade serous or endometrioid
epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer and
resistant platinum relapse with no prior treatment with PLD for their resistant
relapse. Previous treatment with PLD is allowed as long as it was part of one platinum
based regimen and the treatment was finalized at least six months previously to
inclusion in this trial.

- Patients must have platinum-resistant disease, defined as progression within <6 months
from completion of at least 4 cycles of platinum and up to 3 prior chemotherapy
regimens. Patients should have documented treatment-free interval of ≥6 months
following 1st chemotherapy regimen received. Patients with a deleterious mutation in
BRCA are eligible in any case with a resistant relapse including primary resistant
relapse.

- Have measurable disease as defined by RECIST v1.1 Criteria. At least one lesion, not
previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the
longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed
tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate
repeated measurements.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

- Female patients with > 18 years of age.

- Patients must have normal organ and bone marrow function measured within 28 days prior
to administration of study treatment as defined below: Haemoglobin ≥ 10.0 g/dL;
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; No features suggestive of
Myelodysplastic Syndrome/Acute Myeloid Leukemia on peripheral blood smear; White blood
cells (WBC) > 3x109/L; Platelet count ≥ 100 x 109/L; Total bilirubin ≤ 1.5 x
institutional upper limit of normal (ULN); aspartate aminotransferase
(AST/SGOT)/Alaninotransferase (ALT/SGPT) ≤ 2.5 x institutional upper limit of normal
unless liver metastases are present in which case it must be ≤ 5x ULN.

- Patients must have creatinine clearance estimated using the Cockcroft-Gault equation
of ≥51 mL/min. PLD is metabolised by the liver and excreted in the bile. Population
pharmacokinetic data (in the range of creatinine clearance tested of 30-156 ml/min)
demonstrate that PLD clearance is not influenced by renal function. No pharmacokinetic
data are available in patients with creatinine clearance of less than 30 ml/min.

- Patients must have a life expectancy ≥ 16 weeks.

- 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 Postmenopausal is defined as: Amenorrheic for 1 year or more
following cessation of exogenous hormonal treatments; luteinizing hormone (LH) and
follicle stimulating hormone (FSH) levels in the postmenopausal range for women under
50; Radiation-induced oophorectomy with last menses >1 year ago; Chemotherapy-induced
menopause with >1 year interval since last menses; or surgical sterilisation
(bilateral oophorectomy or hysterectomy).

- Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures.

- Left Ventricular Ejection Fraction (LVEF) ≥ 50%.

Exclusion Criteria:

- Platinum-refractory disease (progression during previous platinum therapy).

- Involvement in the planning and/or conduct of the study (applies to both Sponsor staff
and/or staff at the study site).

- Previous enrolment in the present study.

- Participation in another clinical study with an investigational product during the
last 14 days or five half-lives of a drug (whichever is longer) prior to the first
dose of study treatment.

- Any previous treatment with a PARP inhibitor, including olaparib.

- Patients with second primary cancer, except: adequately treated non-melanoma skin
cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for ≥5 years.

- Patients receiving any systemic chemotherapy, radiotherapy (except for palliative
reasons), within 2 weeks from the last dose prior to study treatment (or a longer
period depending on the defined characteristics of the agents used). The patient 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 study
drug.

- Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole,
ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.

- Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by
previous cancer therapy.

- Resting ECG with corrected QT interval (QTc) >470 msec on 2 or more time points within
a 24 hour period or family history of long QT syndrome.

- Blood transfusions within 28 days prior to study entry.

- Patients with myelodysplastic syndrome/acute myeloid leukaemia.

- 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 28
days prior to treatment.

- Major surgery within 14 days of starting study treatment and patients must have
recovered from any effects of any major surgery.

- 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, 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 high-resolution computed tomography (HRCT) scan or
any psychiatric disorder that prohibits obtaining informed consent.

- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study
medication.

- Breast feeding women.

- Immunocompromised patients, e.g., patients who are known to be serologically positive
for human immunodeficiency virus (HIV) and are receiving antiviral therapy.

- Patients with known active hepatic disease (i.e., Hepatitis B or C) due to risk of
transmitting the infection through blood or other body fluids.

- Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.

- Patients with a known hypersensitivity to the combination/comparator agent

- Patients with uncontrolled seizures.

- Previous allogeneic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT).