Epithelial ovarian cancer MedDRA version: 19.0 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Enadenotucirev
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: enadenotucirev
CAS Number: 1402042-02-7
Current Sponsor code: enadenotucirev
Concentration
Sponsors
PsiOxus Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to provide written informed consent and to comply with the study protocol 2. Age = 18 years 3. Histologically confirmed non-resectable epithelial ovarian, fallopian tube or primary peritoneal cancer 4. Phase Ia and Phase Ib first 3 patients: - 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 OR - Absence of other available treatment option Phase Ib (after first 3 patients) and Phase II - 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 Phase Ia and Phase Ib first 3 patients: - Evaluable disease (by RECIST v1.1). Phase Ib (after first 3 patients) and Phase II: - Measurable disease (by RECIST v1.1) 5. Able to undergo IP injection, including all administration procedures e.g. placement of IP catheter, iatrogenic ascites and ascites drainage and comply with study procedures in the Investigator’s opinion 6. Recovered to at least grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancy at time of first administration of enadenotucirev 7. ECOG Performance Status Score of 0 - 1 8. Adequate renal function - Creatinine = 1.8 mg/dl (159 µmol/l) 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+ 9. Adequate hepatic function - Serum bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Tumours of malignant mixed mesodermal (MMMT) or mucinous subtypes, or non-epithelial ovarian cancers (e.g. Brenner tumours, Sex-cord tumours) 2. Symptomatic sub-acute bowel obstruction, characterised by e.g. regular bloating, nausea, vomiting, constipation or diarrhoea 3. Pregnant or lactating (nursing) women 4. Known and/or a history or evidence of significant immunodeficiency due to underlying illness (e.g. human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [AIDS]) and/or medication (e.g. systemic corticosteroids at doses higher than dexamethasone 20 mg [or other corticosteroid equivalent to dexamethasone dose] for 14 days] of dexamethasone at doses higher than 10 mg but 38.0degC associated with a clinical diagnosis of active infection 8. Active viral disease, positive serology for HIV, hepatitis B or hepatitis C 9. Use of the following anti-viral agents: - Ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to day 1 - or pegylated interferon (PEG-IFN) (within 14 days prior to day 1) 10. Administration of an investigational drug within 28 days 11. Concurrent administration of any cancer therapy other than planned study treatment 12. Major surgery within 2 weeks prior to first dose of enadenotucirev 13. Phase Ib (after first 3 patients) and Phase II only: another primary malignancy within the past 3 years (except for non-melanoma skin cancer or cervical cancer in situ or in situ stage 1 synchronous endometrial cancer) 14. Symptomatic central nervous system (CNS) metastasis 15. Inflammatory diseases of the bowel 16. Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease 17. 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 18. Known allergy to treatment medication or its excipients 19. Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ia: - To determine the MTD and/or the dose of enadenotucirev recommended for further studies when administered weekly by IP injection in patients with ovarian cancer Phase Ib: - To determine the MTD and/or the dose of enadenotucirev recommended for further studies when administered by IP injection in combination with weekly IV paclitaxel in patients with ovarian cancer Phase II and Phase Ib patients treated at the dose for Phase II: - To evaluate the PFS of enadenotucirev using RECIST v1.1, when administered by IP injection in combination with weekly IV paclitaxel in patients with recurrent platinum-resistant ovarian cancer;Timepoint(s) of evaluation of this end point: Phase 1a - 28 (±3) days post last Enadenotucirev administration Phase 1b - 28 (±3) days post last Enadenotucirev administration Phase II - 28 (±3) days post last Enadenotucirev administration;Secondary Objective: Phase I only: - Viral kinetics, distribution, clearance and shedding of enadenotucirev - Anti-tumour activity of enadenotucirev in patients with ovarian cancer as measured by response rate, duration of response, clinical benefit rate & PFS Phases I and II: - Safety and tolerability of enadenotucirev in patients with ovarian cancer - Systemic and IP immune response to enadenotucirev Phase II and Ib patients treated at dose recommended for Phase II: - PFS of enadenotucirev in patients with recurrent, platinum-resistant ovarian cancer using irRC and GCIG CA-125 criteria - Anti-tumour activity of enadenotucirev in patients with recurrent, platinum-resistant ovarian cancer, as measured by response rate, duration of response, clinical benefit rate and PFS rate at 4 and 6 months using: RECIST v1.1; irRC criteria; GCIG CA-125 criteria - IP cytological changes including the distribution of inflammatory cell infiltrates and enadenotucirev viral particles in response to enadenotucirev;Primary end point(s): Phase Ia - The maximally-tolerated dose (MTD) and/or the dose of Enade | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability: - Incidence, nature, severity and seriousness of AEs as characterised using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) - Incidence, nature, and severity of changes in laboratory values, vital signs, and physical exam Efficacy: - Response rate, duration of response, clinical benefit rate measured by RECIST v1.1, irRC and CICG criteria, progression free survival measured by RECIST v1.1 irRC, and GCIG CA-125 criteria, PFS rate at 4 and 6 months measured by RECIST v1.1 criteria and irRC Kinetics and immunity: - Describe the kinetics and clearance of Enadenotucirev following administration by IP injection: - Blood kinetics of Enadenotucirev according to qPCR measurement of serial blood samples for Enadenotucirev genome copies and where relevant by plaque assay to determine the presence of viable replicating virus - Viral shedding of Enadenotucirev according to qPCR measurement of buccal and rectal swabs for Enadenotucirev genome copies - Persistence of Enadenotucirev in the peritoneal cavity according to qPCR measurement of serial peritoneal samples for Enadenotucirev genome copies and where relevant by plaque assay to determine the presence of viable replicating virus - Describe the adaptive and innate immune response to Enadenotucirev following administration by IP injection: - Enadenotucirev specific antibody response in blood by enzyme-linked immunosorbent (ELISA) and neutralising assays - Enadenotucirev specific antibody response in peritoneal fluid by ELISA and neutralising assays - Describe the cytokine response in peripheral blood to Enadenotucirev following administration by IP injection by multiplex assay - Describe the pathological changes including cancer cell burden, inflammatory infiltrates and viral particles in biopsies from 2 patients in Phase Ia (treated at the dose to be recommended for Phase II studies as a monotherapy) and 6 patients tr | — |
Countries
Spain, United Kingdom
Contacts
Public ContactProject Manager Cil: 13046
Chiltern International Ltd.
Outcome results
None listed