Phase I / Dose Expansion Study of Enadenotucirev in Ovarian Cancer Patients (OCTAVE)
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This study is a phase I/II open label clinical study in patients with platinum-resistant epithelial ovarian cancer. The Phase I part of the study will determine the dose of enadenotucirev to be recommended for further studies and will examine primarily the safety and tolerability but also the pharmacokinetics of administering enadenotucirev intraperitoneally. Once the dose of IP enadenotucirev to be used in combination with IV weekly paclitaxel has been determined, the phase II stage will begin as an open label dose expansion of that regimen. The phase II stage aims to determine whether intraperitoneal enadenotucirev has a risk benefit profile that supports further investigation in the treatment of patients with platinum-resistant epithelial ovarian Cancer.
Phase I - maximum tolerated dose [ Time Frame: Up to day 50 (post first dose) ]
The maximally-tolerated dose (MTD) and/or the dose of enadenotucirev recommended for further studies of enadenotucirev when administered as monotherapy by IP injection in patients with recurrent, platinum-resistant ovarian cancer.
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Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Able and willing to provide written informed consent and to comply with the study protocol
Age ≥ 18 years
Histologically confirmed non-resectable ovarian, fallopian tube or primary peritoneal cancer
Confirmed relapsed within the platinum-resistant time frame.
Platinum-resistance is defined as progression within 6 months of receiving prior platinum-containing chemotherapy, with progression identified either by CT scanning (RECIST v1.1) or symptomatic CA125 progression (GCIG CA-125 criteria).
The treatment immediately prior to study entry need not be platinum-based.
Measurable disease (by RECIST v1.1).
Able to undergo intraperitoneal injection and comply with study procedures in the Investigator's opinion
Recovered to at least Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancy
ECOG Performance Status Score of 0 - 1
Adequate renal function
Creatinine ≤ 1.8 mg/dL or calculated creatinine clearance using the Cockcroft-Gault formula ≥ 45 mL/min, or measured creatinine clearance ≥ 45 mL/min,
Absence of clinically significant haematuria on urinalysis: dipstick <2+
Absence of clinically significant proteinuria on urinalysis: dipstick < 2+.
Adequate hepatic function
serum bilirubin <1.5 x ULN
AST and ALT ≤ 3 x ULN
Adequate bone marrow function:
ANC ≥ 1.5 x 109/L,
platelets ≥ 100 x 109/L,
haemoglobin ≥ 90 g/L
Adequate coagulation tests: INR ≤ 1.5 x ULN;
Access to archival tumour samples
For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment;
For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year (e.g., hormonal implants, combined oral contraceptives, vasectomized partner), during the treatment period and for at least 3 months after the last dose of study drug;
For patients in the Phase II part of the study participating in the exploratory assessment of tumour samples:
Ovarian Disease amenable to percutaneous image-guided biopsy.
Tumours of malignant mixed mesodermal (MMMT) or mucinous subtypes, or non-epithelial ovarian cancers (e.g. Brenner tumours, Sex-cord tumours).
[Criterion 2 has been removed from the current version of the protocol].
Unresolved bowel obstruction;
Extensive intra-abdominal adhesions and / or tumoural involvement of the small bowel
Pregnant or lactating (nursing) women;
Known and/or a history or evidence of significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids at doses higher than dexamethasone 10 mg or equivalent, or other immunosuppressive medications including cyclosporine, azathioprine, interferons, within the past 4 weeks);
Prior allogeneic or autologous bone marrow or organ transplantation;
Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0 degrees centigrade associated with a clinical diagnosis of active infection;
Active viral disease, positive serology for HIV, hepatitis B or hepatitis C;
Use of the following anti-viral agents:
ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to day 1;
or PEG-IFN (within 14 days prior to day 1);
Administration of an investigational drug within 28 days or within 5 half-lives of first dose of ColoAd1, whichever is longer.
Administration of a systemic cancer therapy within 3 weeks of the first administration of Coload1
Major surgery within 3 weeks or radiotherapy within 3 weeks prior to first dose of ColoAd1;
Another primary malignancy within the past 3 years (except for non-melanoma skin cancer or cervical cancer in situ);
Known CNS metastasis;
Inflammatory diseases of the bowel;
Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.
Any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the drug;
Known allergy to treatment medication or its excipients;
Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.