Phase I/II Study of ColoAd1 Intraperitoneally in Ovarian Cancer Patients

Phase 1

Conditions: Epithelial ovarian cancer
MedDRA version: 18.0Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-001276-38-ES

Lead Sponsor: PsiOxus Therapeutics Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 42

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 EnAd
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 <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 10e9/l
- Platelets ? 100 x 10e9/l
- Haemoglobin ? 90 g/l
11. Adequate coagulation tests: INR ? 1.5 x ULN;
12. Access to archival tumour samples
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 Phase II part of the study participating in the exploratory assessment of tumour samples:
- Ovarian disease amenable to percutaneous image-guided biopsy.
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 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

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. For Phases Ib and II only: Prior treatment with weekly paclitaxel monotherapy within 6 months prior to first dose of EnAd. Prior treatments with other schedules of paclitaxel or combination chemotherapy including weekly paclitaxel are accepted
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. Splenectomy
7. Prior allogeneic or autologous bone marrow or organ transplantation
8. Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0degC 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 EnAd
14. 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)
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.