Phase I/II clinical trial of ColoAd1 by sub-acute fractionated IV dosing in cancer patients

Phase 1

Conditions: metastatic colorectal cancer
MedDRA version: 18.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-001067-79-BE

Lead Sponsor: Psioxus Therapeutics Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 173

Inclusion Criteria

INCLUSION CRITERIA FOR ALL PATIENTS
1. Patients must provide written informed consent
2. Age = 18 years and the patient must be at least the legal age limit to be able to give consent within the jurisdiction the study is taking place.
3. ECOG performance status 0 or 1
4. Predicted life expectancy of 3 months or more
5. Ability to comply with study procedures in the Investigator's opinion
6. Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies.
7. Adequate renal functions
a. Creatinine = 1.5 mg/dL or calculated creatinine clearance using the Cockcroft-Gault formula = 60 mL/min, or measured creatinine clearance =60 mL/min
b. Urine dipstick for proteinuria < 2+ or proteinuria 0.75g / 24 hours
8. Adequate hepatic function:
a. Serum bilirubin <1.5 mg/dL
b. Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 x ULN
9. Adequate bone marrow function:
a. Absolute neutrophil count (ANC) = 1.5 x 109/L,
b. Platelets = 100 x 109/L
c. Haemoglobin = 100 g/L for UCC and = 90 g/L for other cancers
10. Adequate coagulation tests: INR = 1.5 x ULN;
11. For females of childbearing potential (defined as <2 years after last menstruation or not surgically sterile), a negative serum pregnancy test must be documented within 14 days prior to first administration of study treatment;
12. For women who are not postmenopausal (24 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception, during the treatment period
and for at least 3 months after the last dose of study drug.13. For men: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug
14. At least 3 weeks since the last dose of any intravenous systemic chemotherapy and at least two weeks since the last oral dose of
capecitabine at time of first administration of ColoAd1.

For Phase 1 Dose Escalation Stage only (except Repeat Cycle Cohort):
15. Solid tumour of epithelial origin not responding to standard therapy or for whom no standard treatment exists

For Phase 1 Dose Expansion Stage Single Cycle and Dose Escalation Stage Repeat Cycle Cohort:
16. Metastatic colorectal carcinoma not responding to standard therapy,
17. = 3 prior lines of systemic therapy for advanced disease OR = 4 prior lines of systemic therapy for advanced disease if one of the 4 lines was an anti-EGFR therapy given as a single agent or combined to a previously administered chemotherapy regimen;

For Phase Ib:
18. mCRC not responding to standard therapy with no more than 3 prior lines of systemic therapy for advanced disease OR no more than 4 prior lines of systemic therapy for advanced disease if one of the 4 lines was an anti EGFR therapy given as a single agent or combined to a previously administered chemotherapy regimen
OR
Advanced or metastatic UCC not a candidate for chemotherapy

For Phase 2:
19. Metastatic colorectal cancer;
20. Have received 3 - 4 months of first line chemotherapy with either FOLFOX, FOLFIRI or CAPOX, with or without bevacizumab;
21. At least one measurable lesion according to RECIST 1.1 criteria;
22. Documented partial response or stable disease;
23. Eligible to receive chemotherapy with FOLFOX or CAPOX after a short chemotherapy interruption (3-4 weeks)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 ye

Exclusion Criteria

For all patients:
1. Pregnant or breast feeding females
2.Known history or evidence of significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic
corticosteroids, or other immunosuppressive medications including cyclosporine, azathioprine, interferons, within the past 4 weeks)
3. Splenectomy
4. Prior allogeneic or autologous bone marrow or organ transplantation
5. Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0 degrees centigrade associated with a clinical
diagnosis of active infection
6. Active viral disease or known positive serology for HIV, hepatitis B or hepatitis C
7. 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 first administration of ColoAd1)
8. Administration of an investigational drug within 28 days prior to first dose of ColoAd1
9. Major surgery within 4 weeks or radiotherapy within 3 weeks prior to first dose of ColoAd1
10. Another primary malignancy within the past 3 years (except for nonmelanoma skin cancer or cervical cancer in situ)
11. CNS metastasis that is symptomatic and/or requires treatment
12. 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
13. Known allergy to treatment medication or its excipients
14. Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
For Phase 2 patients:
15. Progression on first line therapy
16. A complete response on first line therapy
17. Use of first line therapy for longer than 4 months
18. Use of any first line treatment with a chemotherapy regimen other than FOLFOX, FOLFIRI or CAPOX (with or without bevacizumab).
19. More than 6 weeks since the last administration of 5 FU, capecitabine, oxaliplatin or irinotecan.