Olaparib and Pegylated Liposomal Doxorubicin for Platinum Resistant Ovarian Primary Peritoneal Carcinoma, and Fallopian Tube Cancer patients.
- Conditions
- Platinum resistant ovarian primary peritoneal carcinoma, and fallopian tube cancer patients.MedDRA version: 20.0Level: PTClassification code 10070908Term: Ovarian cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10057529Term: Ovarian cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004850-14-ES
- Lead Sponsor
- Grupo Español de Investigación en Cancer de Ovario
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 32
1. 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.
2. 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.
3. 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.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status =2.
6. Female patients with > 18 years of age.
7. 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.
8. Patients must have a life expectancy = 16 weeks.
9. 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).
10. Patient is willing and able to comply with the prot
1. Platinum-refractory disease (progression during previous platinum therapy).
2. Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study site).
3. Previous enrolment in the present study.
4. 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.
5. Any previous treatment with a PARP inhibitor, including olaparib.
6. 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.
7. 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.
8. Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin
and nelfinavir.
9. Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
10. 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.
11. Blood transfusions within 28 days prior to study entry.
12. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
13. 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.
14., Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery.
15. 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.
16. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
17. Breast feeding women.
18. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are
receiving antiviral therapy.
19. 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.
20. Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
21. Patients with a known hypersensitivity to the combination/comparator agent
22. Patients with uncontrolled seizures.
23. Previous allogeneic bone marrow transplant or double umbilical cord blood tr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of the addition of Olaparib to PLD in platinum resistant advanced ovarian cancer patients plus maintenance with Olaparib. The primary endpoint is 6 months progression-free survival rate (PFS6m).;Secondary Objective: Secondary Objective(s):<br>- Objective Response Rate.<br>- Disease Control Rate.<br>- Response to treatment according CA-125 levels.<br>- Progression-free survival.<br>- Overall survival.<br>- Health related quality of life.<br>- Activity of tumor based on the growth modulation index (GMI).<br><br>Safety Objective:<br>To determine the safety and tolerability of olaparib in combination with PLD and as monotherapy in platinum resistant advanced ovarian cancer.;Primary end point(s): 6 months progression-free survival rate (PFS6m).;Timepoint(s) of evaluation of this end point: Six months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Objective Response Rate<br>- Disease control rate<br>- Reponse to treatment according CA-125 levels.<br>- Progression-free survival at the end of follow up.<br>- Overall survival<br>- Health related quality of life<br>- Activitity of tumour based on the GMI.<br>- Safety endpoints <br>-Translational subestudies;Timepoint(s) of evaluation of this end point: Patients will be visited according the following schema: <br>1. Every week during the first month of treatment.<br>2. Every 2 weeks during the second month of treatment.<br>3. Every 4 weeks from 3 up to 12 months (calculated from first study treatment<br>administration).<br>4. Every 12 weeks up to 2 years calculated from first study treatment administration.<br>5. According local normal clinical practise from 2 years until exitus<br>Furthermore, the following visits should be done when applicable:<br>6. At the end of study treatment.<br>7. Safety visit (after 30 days of end of treatment).