A study, performed in several centers, to examine the treatment combination of cediranib-olaparib at the time of disease progression in ovarian cancer after use of PARP inhibitor treatment.

Phase 1

• Conditions: Clinical trial of the combination cediranib-olaparib at the time of disease progression on PARP inhibitor in ovarian cancer.; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001192-23-ES
• Lead Sponsor: niversity Health Network, Toronto

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-12
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

1. Age = 18 years
2. Performance status = 2 within 7 days of registration
3. Histologically confirmed ovarian , fallopian tube or primary peritoneal cancer, high grade serous or high grade endometrioid histology subtype.
4. Radiographically documented disease progression within 28 days of registration and evaluable as per RECIST 1.1
5. Progression on any PARP inhibitor therapy (example: olaparib) that meet one of the following criteria:
i) Platinum sensitive with no evidence of disease progression within 6 months of the last dose of platinum based chemotherapy and received PARP inhibitor treatment as their last line of treatment.
Or
ii) Platinum resistance with disease progression within 6 months of the last dose of a platinum based chemotherapy and received PARP inhibitor as their last line of treatment. Patients are allowed to have received other treatments in between platinum based chemotherapy and PARP inhibitor treatment.
Or
iii) Disease progression on PARP therapy who then received standard chemotherapy with further disease progression.
6. Patients must have adequate bone marrow, renal and hepatic function per local laboratory reference range as follows within 7 days of registration:
i) Absolute Neutrophil Count = 1.5 x 109/L;
ii) Platelets = 100 x 109/L;
iii) Hemoglobin = 10.0g/dL;
Renal function:
iv) Calculated creatinine clearance >50mL/min (Cockcroft formula);
v) AST/ALT = 2.5× the upper limit of normal (ULN); Subjects with liver metastasis may have AST, ALP, and ALT = 5.0 XULN;
vi) Bilirubin = 1.5×ULN
7. LVEF > 50% by echocardiograms or MUGA within 28 days of registration
8. Patients are willing to undergo tumour biopsy pre-treatment. If a biopsy at the time of progression on PARP therapy is available and can be submitted to the Central Lab for this study, this procedure does not need to be repeated. Patients who consent but have tumour that is not amenable to safe biopsy will be allowed to enter the trial and continue therapy as per protocol if this has been addressed and permission is granted from the Sponsor , Dr. Amit Oza prior to registration.
9. Life expectancy of greater than 3 months
10.Ability to understand and the willingness to sign a written informed consent document
11.Subject is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
12.Patients of child bearing potential and their partners who are sexually active (exception: abstinence) must agree to the use of 2 highly effective forms of contraception throughout their participation during the study treatment and for 3 months after last dose of study treatment(s)
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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. Patients with current bowel obstruction.
2. Untreated unstable brain or meningeal metastases or tumour. Patients with radiological evidence of stable brain metastases are eligible providing that they are asymptomatic and either do not require corticosteroids or have been treated with corticosteroids, with clinical and radiological evidence of stabilization at least 10 days after discontinuation of steroids.
3. Greater than +1 proteinuria on two consecutive dipsticks within 14 days of registration taken no less than 1 week apart unless urinary protein < 1.5g in a 24h period or urine protein/creatinine ratio < 1.5.
4. Unresolved toxicity > CTCAE grade 1 from previous anti-cancer therapy (including radiotherapy) except haematological toxicity (see inclusion 6) and alopecia.
5. History of poorly controlled hypertension or resting blood pressure > 150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy within 7 days of registration (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, than an additional reading should be obtained and averaged).
6. Mean QTc >470 msec (with Bazett’s correction) in screening electrocardiograms within 7 days of registration or history of familial long QT syndrome.
7. Any evidence of severe or uncontrolled diseases such as but not limited to unstable or uncompensated respiratory, cardiac, hepatic, renal disease or psychiatric illness/social situations that would limit compliance with study requirements.
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or cediranib.
9. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
10. Treatment with an investigational (non-
registered – other than PARP inhibitor) drug within 30 days and treatment with PARP inhibitor within 14 days prior to the first dose of study medication
11.Patients with myelodysplastic syndrome/acute myeloid leukaemia.
12.Previous allogenic bone marrow transplant.
13.Immuno-compromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
14.Patients who require maximal doses of calcium channel blockers to stabilize blood pressure.
15.Patients with significant hemorrhage (>30 mL bleeding/episode in previous 3 months) or haemoptysis (>5 mL fresh blood in previous 4 weeks).
16.Patients who have had recent (within 2 weeks of registration, or until any wound has completely healed) major thoracic or abdominal surgery prior to study start, or a surgical incision that is not fully healed.
17.History of stroke or transient ischemic attack within six months.
18.Patients that are receiving and cannot stop the following prohibited medications prior to Cycle 1, Day 1;
i) CYP3A4 inhibitors such as but not limited to; Ketoconazole, Itraconazole, Ritonavir, Indinavir, Saquinavir, Telithromycin, Clarithromycin & Nelfinavir
ii) CYP3A4 inducers such as but not limited to; Phenytoin, Rifampicin, Rifapentin, Rifabutin, Carbamazepine, Phenobarbital, Nevirapine, Modafinil & St. John’s Wort (Hypericum

Study & Design

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