| Eligibility |
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 CA-125 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 Dose Expansion Phase:
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 CA-125 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 Dose Expansion Phase:
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 (only required for patients scheduled for IP
administration)
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. Non-impaired renal function
• Creatinine =1.5 mg/dl and estimated glomerular filtration rate (eGFR) =60
mL/min/1.73m2 (or measured creatinine clearance =60 ml/min)
9. Urine dipstick for proteinuria at screening and baseline negative or trace. Patients
may be included with results of 1+ if they have a spot urinary albumin:creatinine
ratio (ACR) of either (i) =3 mg/mmol or (ii) >3 mg - <70 mg/mmol with a 24 hour
urinary protein <0.2 g/24hours Adequate hepatic function
- Serum bilirubin <1.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) =3 x ULN
10. Adequate bone marrow function:
- Absolute neutrophil count (ANC) =1.5 x 109/l
- Platelets =100 x 109/l
- Haemoglobin =90 g/l
11. Adequate coagulation tests: INR =1.5 x ULN;
12. [Criterion has been removed in the current version of the protocol]
13. For females of childbearing potential, a negative pregnancy test must be documented
prior to enrolment
14. 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, vasectomised partner), during
the treatment period and for at least 3 months after the last dose of study drug
15. For selected patients in the Phase Ia and Dose Expansion Phase part of the study
participating in the exploratory assessment of tumour samples:
• Disease amenable to percutaneous image-guided biopsy.
16. Normal serum complement (C3/C4)
Exclusion Criteria:
Patients who meet any of the following criteria are not eligible for enrolment:
1. Tumours of malignant mixed mesodermal (MMMT) or mucinous subtypes, or non-epithelial
ovarian cancers (e.g. Brenner tumours, Sex-cord tumours)
2. [Criterion 2 has been removed in the current version of the protocol]
3. Symptomatic sub-acute bowel obstruction, characterised by e.g. regular bloating,
nausea, vomiting, constipation or diarrhoea
4. Pregnant or lactating (nursing) women
5. 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 or prolonged administration [>14 days] of dexamethasone at doses higher than 10
mg but 20 mg [or other corticosteroid equivalent to dexamethasone dose] or other
immunosuppressive medications including cyclosporine, azathioprine, interferons,
within the past 14 days)
6. Complete splenectomy
7. Prior allogeneic or autologous bone marrow or organ transplantation
8. Active infections requiring antibiotics, physician monitoring, or recurrent fevers
>38.0 degrees centigrade associated with a clinical diagnosis of active infection
9. Active viral disease, positive serology for HIV, hepatitis B or hepatitis C
10. 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)
11. Administration of an investigational drug within 28 days
12. Concurrent administration of any cancer therapy other than planned study treatment
13. Major surgery within 2 weeks prior to first dose of enadenotucirev
14. Phase Ib (after first 3 patients) and Dose Expansion Phase 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)
15. Symptomatic central nervous system (CNS) metastasis
16. Inflammatory diseases of the bowel
17. Concurrent congestive heart failure or prior history of New York Heart Association
(NYHA) class III/IV cardiac disease
18. 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
19. Known allergy to treatment medication or its excipients
20. Any other medical or psychological condition that would preclude participation in the
study or compromise ability to give informed consent.
21. Any history of renal disease or renal injury or autoimmune disease. Patients with
active, known or suspected auto-immune disease or a syndrome that requires systemic or
immunosuppressive agents; patients with vitiligo, type I diabetes mellitus, residual
hypothyroidism due to autoimmune disease only requiring hormone replacement, psoriasis
not requiring systemic treatment or conditions not expected to recur in the absence of
an external trigger are permitted to enrol providing they comply with the other
eligibility criteria relating to renal function)
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