Ovarian Cancer
Conditions
Brief summary
A research study evaluating a new oncolytic virus, THEO-260, in patients with advanced ovarian cancer. The trial will investigate different doses of THEO-260 administered intravenously to identify a dose that is safe, well tolerated, and exhibits preliminary evidence of anti tumour activity.
Interventions
BIOLOGICALTHEO-260
Oncolytic Virus
Sponsors
Theolytics Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed histological diagnosis of advanced high grade serous or endometrioid cancer of the fallopian tube, primary peritoneum or ovary either on archival biopsy or fresh tumour biopsy. * Platinum-resistant disease (radiological recurrence/ progression with 6 months of prior platinum treatment), primary platinum-refractory disease (recurrence/ progression during first line platinum treatment) and patients who are intolerant to or have no available SOC or SOC unacceptable/ unsuitable in the view of the Investigator. * Life expectancy of \> 3 months. * ECOG performance status of 0 or 1. * Measurable disease as per RECIST V1.1.
Exclusion criteria
* Prior anti-cancer treatment within 28 days or 5 half-lives, prior to first dose of THEO-260. * Prior treatment with a group B adenovirus. * Currently enrolled in a clinical trial of an IMP or used any IMP with 5 half-live, prior to first dose of THEO-260. * Radiation therapy within 2 weeks of first dose of THEO-260 and is scheduled to have radiation therapy during participation of trial. * Clinical evidence of cerebral metastases or Central Nervous System (CNS) involvement including leptomeningeal disease. Patients with previous cerebral metastases must have no evidence of progression or haemorrhage after treatment. * Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures (as defined as once monthly or more frequently). * Prior pneumonitis or history of interstitial lung disease. * Confirmed QTcF ≥470 ms on screening 12-lead ECG or history of Torsades de Pointes or history of congenital long QT syndrome. * Concomitant medications that prolong the QTc interval and/or increase the risk for Torsades de Pointes. * Patients with active hepatitis infection or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection. * Active infection with tuberculosis. * Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). * Patients with active human immunodeficiency virus (HIV) infection or known history of HIV infection. * Active infection requiring IV antibiotics within 2 weeks prior to first dose of THEO-260, or long-term oral therapy for systemic infection. * Known contra-indications or hypersensitivity to the excipients of the IMP. * Viral infection during the 2 weeks prior to first dose of THEO-260. * Active autoimmune disease that has required systemic treatment in the past 2 years. * Known risk of renal injury, including those with a past history of acute or sub-acute renal disease. * Known heart failure New York Heart Association (NYHA) Class 2-4. * Known contra-indications or hypersensitivity to the AxMP, paracetamol. * Known alcohol consumption in excess of 2 units per day. * Left ventricular ejection fraction (LVEF) \<50%, unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to trial enrolment or a history of myocarditis. * Arterial oxygen saturation \<92% on room air prior to first dose of THEO-260. * Received any licensed or investigational vaccines within 28 days prior to first dose of THEO-260.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of THEO-260 [Part A] | Until Day 28 after first dose | Assessment of DLTs and AEs during treatment and follow-up using NCI CTCAE v5.0 or ASCO (for pneumonitis only) or ASTCT (for CRS only), plus Laboratory parameters and clinical safety assessments. |
| Establish recommended Phase 2 dose (RP2D) for THEO-260 [Part A] | Estimated at 2 years | Determination of RP2D will be based on the totality of safety, PK and preliminary efficacy data |
| Evaluate preliminary efficacy of THEO-260 [Part B] | Estimated at 16 weeks | Determine tumour response by RECIST v1.1 and iRECIST and changes in CA-125. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of THEO-260 | Estimated at 16 weeks | Assess PK parameters of THEO-260 |
| Shedding of THEO-260 | Until Day 29 after first dose | Detection of THEO-260 in buccal, urine and faecal samples |
| Systemic CRS risk after THEO-260 | Until Day 29 after first dose | Incidence and severity of CRS, measurement by key cytokines/biomarkers in blood. |
| Preliminary efficacy of THEO-260 [Part A] | Estimated at 16 weeks | Determine tumour response by RECIST v1.1 and iRECIST, changes in CA-125 and patient reported outcomes using EORTC QoL questionnaires |
| Safety and tolerability of THEO-260 [Part B] | Until end of trial, estimated at 1 year after start of enrolment | Assessment of AEs during treatment and follow-up using NCI CTCAE v5.0 or ASCO (for pneumonitis only) or ASTCT (for CRS only), plus Lab oratory parameters and clinical safety assessments. |
Countries
Spain, United Kingdom
Contacts
CONTACTClinical Trials
Outcome results
None listed