resistant high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. MedDRA version: 21.1 Level: PT Classification code 10070907 Term: Ovarian cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10070908 Term: Ovarian cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cediranib
Product Code: [Not Applicable]
Pharmaceutical Form: Tablet
INN or Proposed INN: 8764
CAS Number: 288383-20-0
Current Sponsor code: AZD2171
Concentration unit: mg milligram(s)
C
Sponsors
IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients affected by pathologically confirmed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. 2.Relapsed/progressive disease within 6 months from last platinum-based chemotherapy (platinum resistant/refractory disease) 3.Any line of treatment (after the first). 4.Any “last” chemotherapy line, including Paclitaxel that should have been administered at least 6 months before the study beginning. 5.Patients must be women > 18 years of age. 6.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 and no blood transfusions in the 28 days prior to entry/randomisation - Absolute neutrophil count (ANC) = 1.5 x 109/L - White blood cells (WBC) > 3x109/L - Platelet count = 100 x 109/L - Total bilirubin = 1.5 x institutional upper limit of normal (ULN) - AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be = 5x ULN - Creatinine clearance estimated using the Cockcroft-Gault equation of =51 mL/min using the Cockcroft-Gault equation. 7.ECOG performance status 0-1 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 (delete if male population) or postmenopausal women. Postmenopausal is defined as: -Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, -LH and FSH levels in the post-menopausal range for women under 50, -Radiation-induced oophorectomy with last menses >1 year ago, -Chemotherapy-induced menopause with >1 year interval since last menses -Surgical sterilization (bilateral oophorectomy or hysterectomy). 10.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. 11.At least one lesion (measurable as defined by RECIST 1.1) that can be accurately assessed by CT scan or MRI with Chest X-ray at baseline and follow up visits. 12.BRCA1-2 mutation status known 13.Provision of informed consent prior to any study specific procedures. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Any previous treatment with a PARP inhibitor, including Olaparib. 2.Prior treatment with Cediranib (previous bevacizumab or other antiangiogenic drugs are allowed) 3.Previous progression to weekly Paclitaxel 4.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 5.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 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. 6.Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting Olaparib is 2 weeks. 7.Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting Olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. 8.Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy. 9.Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. 10.Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein 150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy (measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2-minute intervals and averaged. If the first two diastolic readings differ by more than 5 mmHg, then an additional reading should be obtained and averaged) 12.Blood transfusions within 28 days prior to study start 13.Features suggestive of Myelodysplastic syndrome or Acute myeloid leukemia (MDS/AML) on peripheral blood smear. 14.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. 15.Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 16.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 HRCT scan or any psychiatric disorder that prohibits obtaining informed consent. 17.Patients unable to swallow medications and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 18.Breast feeding women. 19.Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy. 20.K
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to evaluate and to compare the efficacy of the combination of Olaparib and Cediranib to the efficacy of weekly Paclitaxel administration, in terms of time to disease progression. The study has also as main objective the safety evaluation of the new intermittent schedule of Cediranib compared to the administration of Cediranib with continuous schedule in terms of gastro-intestinal toxicity. ;Secondary Objective: Secondary efficacy objectives will be the evaluation of treatment response, the prolongation of the time to second progression, overall survival and quality of life. Other study aims will be to assess the safety and tolerability of combination of Olaparib and Cediranib vs. paclitaxel as single agent chemotherapy and the compliance to the study treatments. ;Primary end point(s): The study primary endpoint will be the progression free survival (PFS) defined as the time from randomization to the date of first progression or death for any cause, whichever comes first. Progression will be established as the radiological disease progression according to RECIST 1.1 or to clinical assessment in case radiological evaluation is not feasible due to clinical condition. The primary endpoint for safety will be the number of evacuations per day. ;Timepoint(s) of evaluation of this end point: Disease progression will be evaluated at the end of every 8 weeks (+/- 1 week) from randomisation for 48 weeks and every 12 weeks (+/- 1 week) thereafter. Safety primary endopoint: number of evacuations will be recorded by the patients every day during whole treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be: - Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1 - PFS2 defined as time from randomization to second disease progression according to RECIST 1.1 or to clinical assessment, or death by any cause. - Overall Survival (OS), defined in each patient as the time from randomization to the date of death for any cause. - Quality of Life evaluated by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire. Secondary endpoints of safety will be: - the maximum toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE v. 4.0; - the number of patients experiencing grade 3-4 toxicity for each toxicity; - type, frequency and nature of SAEs; - patients with at least a SAE; patients with at least a SADR; - patients with at least a SUSAR. The endpoints for compliance will be: number of administered cycles, reasons for discontinuation and treatment modification and dose intensity. ;Timepoint(s) of evaluation of this end point: Efficacy: second disease progression evaluated every 12 weeks from first progression. ORR according to radiological disease assessment, performed every 8 weeks from random until the end of treatment and every 12 weeks thereafter. Survival evaluated every 12 weeks from the first disease progression until overall survival analysis. Quality of life data recorded during baseline visit and every 4 weeks for the first 6 months or until treatment discontinuation whichever come first. Safety: toxicities occurred during treatment period and the fist 30 days from the date of last treatment administration Compliance endopoints will be recorded during whole treatment period. | — |
Countries
Italy
Contacts
Public ContactLaboratorio Metodologia della Ricer
IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”
Outcome results
None listed