Phase I / II Study of Enadenotucirev by Sub-acute Fractionated IV Dosing in Cancer Patients (EVOLVE)
Primary Purpose
Solid Tumours of Epithelial Origin, Metastatic Colorectal Cancer, Metastatic Bladder Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Enadenotucirev
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumours of Epithelial Origin
Eligibility Criteria
Inclusion Criteria:
- Patients must provide written informed consent
- 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.
- ECOG performance status 0 or 1
- Predicted life expectancy of 3 months or more
- Ability to comply with study procedures in the Investigator's opinion
- Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
Adequate renal function
- Creatinine ≤ 1.5 mg/dL or calculated creatinine clearance using the Cockcroft-Gault formula ≥ 60 mL/min, or measured creatinine clearance ≥ 60 mL/min, Haematuria: dipstick ≤ 2+
- Proteinuria: dipstick ≤ 2+
Adequate hepatic function
- Serum bilirubin < 1.5 mg/dL
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3x upper limit of normal (ULN)
Adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Haemoglobin ≥ 100 g/L for UCC and ≥ 90 g/L for other cancers
- Adequate coagulation tests: international normalised ratio (INR) ≤ 1.5 x ULN
- 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
- 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
- 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
- At least 3 weeks since any dose of IV systemic chemotherapy and at least two weeks since any oral dose of capecitabine at the time of first administration of ColoAd1.
Phase I Specific Inclusion Criteria:
Dose Escalation Stage only (except Repeat Cycle Cohort):
- Solid tumour of epithelial origin not responding to standard therapy or for whom no standard treatment exists
Dose Expansion Stage Single Cycle and Dose Escalation Stage Repeat Cycle Cohort:
- mCRC not responding to standard therapy
- ≤ 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 Phase Ib:mCRC not responding to standard therapy
- 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
- Advanced or metastatic UCC, who have received a maximum of one chemotherapy-containing regimen and a maximum of one other systemic treatment with biologic agents only.
Phase II Specific Inclusion Criteria:
- mCRC
- Have received 3 - 4 months of first line chemotherapy with either FOLFOX, FOLFIRI or CAPOX, with or without bevacizumab
- At least one measurable lesion according to RECIST 1.1 criteria
- Documented partial response or stable disease
- Eligible to receive chemotherapy with FOLFOX or CAPOX after a short chemotherapy interruption (3 to 4 weeks)
Exclusion Criteria for all Patients:
- Pregnant or breast feeding females;
- Known 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, or other immunosuppressive medications including cyclosporine, azathioprine, interferons, within the past 4 weeks)
- Splenectomy
- Prior allogeneic or autologous bone marrow or organ transplantation
- Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0 degrees centigrade associated with a clinical diagnosis of active infection
- Active viral disease or known positive serology for HIV, hepatitis B or hepatitis C;
- 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 first administration of ColoAd1)
- Administration of an investigational drug within 28 days prior to first dose of ColoAd1
- Major surgery within 4 weeks or radiotherapy within 3 weeks prior to first dose of ColoAd1
- Another primary malignancy within the past 3 years (except for non melanoma skin cancer or cervical cancer in situ)
- Central nervous system (CNS) metastasis that is symptomatic and/or requires treatment
- 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
- Known allergy to treatment medication or its excipients
- Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Phase II Specific Exclusion Criteria:
- Progression on first line therapy
- A complete response on first line therapy
- Use of first line therapy for longer than 4 months
- Use of any first line treatment with a chemotherapy regimen other than FOLFOX, FOLFIRI or CAPOX (each with or without bevacizumab)
- More than 6 weeks since the last administration of 5 FU, capecitabine, oxaliplatin or irinotecan
Sites / Locations
- GZA ziekenhuizen campus Sint-Augustinus
- Cliniques Universitaires St Luc
- Ghent University Hospital
- Institut Catala d Oncologica
- START - Hospital Universitario Madrid Sanchinarrio
- Hospital Universitario Virgen del Rocio (HUVR)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Enadenotucirev
Arm Description
Outcomes
Primary Outcome Measures
Phase 1 - Maximum Tolerated Dose
- Maximum tolerated dose (MTD) / maximum feasible dose (MFD) of enadenotucirev when administered by sub-acute fractionated IV injection (phase I Dose Escalation) and recommended dose for phase II.
Phase 1b - Selection of suitable schedule for repeat cycle IV administration
Open label assessment of 2 repeat cycle schedules, with expansion cohort at the MTD or MFD with best repeat cycle schedule in advanced/metastatic UBC patients.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02028442
Brief Title
Phase I / II Study of Enadenotucirev by Sub-acute Fractionated IV Dosing in Cancer Patients
Acronym
EVOLVE
Official Title
A Clinical Study Of Enadenotucirev Administered by Sub-Acute Fractionated Intravenous Injection: Dose Escalation in Metastatic Epithelial Solid Tumours and Randomised Controlled Trial in Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
September 20, 2012 (Actual)
Primary Completion Date
April 29, 2016 (Actual)
Study Completion Date
April 29, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akamis Bio
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multicentre, open-label, Phase I/II study of enadenotucirev in patients with either solid tumour of epithelial origin not responding to standard therapy or for whom no standard treatment exists (Phase I dose escalation stage Single cycle), mCRC not responding to standard therapy (Phase I dose escalation Repeat cycle cohort expansion stage ), mCRC not responding to standard therapy or advanced or metastatic bladder cancer not candidate for chemotherapy (Phase Ib) or mCRC in stable disease or partial response after 3-4 months of first line standard of care chemotherapy (Phase II).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumours of Epithelial Origin, Metastatic Colorectal Cancer, Metastatic Bladder Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Enadenotucirev
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Enadenotucirev
Intervention Description
Oncolytic virus
Primary Outcome Measure Information:
Title
Phase 1 - Maximum Tolerated Dose
Description
- Maximum tolerated dose (MTD) / maximum feasible dose (MFD) of enadenotucirev when administered by sub-acute fractionated IV injection (phase I Dose Escalation) and recommended dose for phase II.
Time Frame
Up to Day 22
Title
Phase 1b - Selection of suitable schedule for repeat cycle IV administration
Description
Open label assessment of 2 repeat cycle schedules, with expansion cohort at the MTD or MFD with best repeat cycle schedule in advanced/metastatic UBC patients.
Time Frame
Up to Day 134
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must provide written informed consent
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.
ECOG performance status 0 or 1
Predicted life expectancy of 3 months or more
Ability to comply with study procedures in the Investigator's opinion
Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
Adequate renal function
Creatinine ≤ 1.5 mg/dL or calculated creatinine clearance using the Cockcroft-Gault formula ≥ 60 mL/min, or measured creatinine clearance ≥ 60 mL/min, Haematuria: dipstick ≤ 2+
Proteinuria: dipstick ≤ 2+
Adequate hepatic function
Serum bilirubin < 1.5 mg/dL
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3x upper limit of normal (ULN)
Adequate bone marrow function:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Platelets ≥ 100 x 109/L
Haemoglobin ≥ 100 g/L for UCC and ≥ 90 g/L for other cancers
Adequate coagulation tests: international normalised ratio (INR) ≤ 1.5 x ULN
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
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
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
At least 3 weeks since any dose of IV systemic chemotherapy and at least two weeks since any oral dose of capecitabine at the time of first administration of ColoAd1.
Phase I Specific Inclusion Criteria:
Dose Escalation Stage only (except Repeat Cycle Cohort):
- Solid tumour of epithelial origin not responding to standard therapy or for whom no standard treatment exists
Dose Expansion Stage Single Cycle and Dose Escalation Stage Repeat Cycle Cohort:
mCRC not responding to standard therapy
≤ 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 Phase Ib:mCRC not responding to standard therapy
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
Advanced or metastatic UCC, who have received a maximum of one chemotherapy-containing regimen and a maximum of one other systemic treatment with biologic agents only.
Phase II Specific Inclusion Criteria:
mCRC
Have received 3 - 4 months of first line chemotherapy with either FOLFOX, FOLFIRI or CAPOX, with or without bevacizumab
At least one measurable lesion according to RECIST 1.1 criteria
Documented partial response or stable disease
Eligible to receive chemotherapy with FOLFOX or CAPOX after a short chemotherapy interruption (3 to 4 weeks)
Exclusion Criteria for all Patients:
Pregnant or breast feeding females;
Known 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, or other immunosuppressive medications including cyclosporine, azathioprine, interferons, within the past 4 weeks)
Splenectomy
Prior allogeneic or autologous bone marrow or organ transplantation
Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0 degrees centigrade associated with a clinical diagnosis of active infection
Active viral disease or known positive serology for HIV, hepatitis B or hepatitis C;
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 first administration of ColoAd1)
Administration of an investigational drug within 28 days prior to first dose of ColoAd1
Major surgery within 4 weeks or radiotherapy within 3 weeks prior to first dose of ColoAd1
Another primary malignancy within the past 3 years (except for non melanoma skin cancer or cervical cancer in situ)
Central nervous system (CNS) metastasis that is symptomatic and/or requires treatment
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
Known allergy to treatment medication or its excipients
Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Phase II Specific Exclusion Criteria:
Progression on first line therapy
A complete response on first line therapy
Use of first line therapy for longer than 4 months
Use of any first line treatment with a chemotherapy regimen other than FOLFOX, FOLFIRI or CAPOX (each with or without bevacizumab)
More than 6 weeks since the last administration of 5 FU, capecitabine, oxaliplatin or irinotecan
Facility Information:
Facility Name
GZA ziekenhuizen campus Sint-Augustinus
City
Wilrijk
State/Province
Antwerp
ZIP/Postal Code
B-2610
Country
Belgium
Facility Name
Cliniques Universitaires St Luc
City
Bruxelles
ZIP/Postal Code
B-1200
Country
Belgium
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Institut Catala d Oncologica
City
Barcelona
ZIP/Postal Code
08970
Country
Spain
Facility Name
START - Hospital Universitario Madrid Sanchinarrio
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio (HUVR)
City
Seville
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
30691536
Citation
Machiels JP, Salazar R, Rottey S, Duran I, Dirix L, Geboes K, Wilkinson-Blanc C, Pover G, Alvis S, Champion B, Fisher K, McElwaine-Johnn H, Beadle J, Calvo E. A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE). J Immunother Cancer. 2019 Jan 28;7(1):20. doi: 10.1186/s40425-019-0510-7.
Results Reference
derived
Links:
URL
https://jitc.bmj.com/content/7/1/20
Description
Journal publication for EVOLVE study
Learn more about this trial
Phase I / II Study of Enadenotucirev by Sub-acute Fractionated IV Dosing in Cancer Patients
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