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Solid Tumours of Epithelial OriginPhase 1/2EVOLVENCT02028442

Phase I / II Study of Enadenotucirev by Sub-acute Fractionated IV Dosing in Cancer Patients

A Phase 1/2 study testing Enadenotucirev in people with Solid Tumours of Epithelial Origin and Metastatic Colorectal Cancer, run by Akamis Bio at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Enadenotucirev
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
6 sitesin 2 countries
Study dates
20 Sep 2012to 29 Apr 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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;
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  • 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

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Belgium3 sites

  • Cliniques Universitaires St Luc

    Brussels, B-1200

  • Ghent University Hospital

    Ghent, 9000

  • GZA ziekenhuizen campus Sint-Augustinus

    Wilrijk, Antwerp, B-2610

Other trials in Belgium

Spain3 sites

  • Institut Catala d Oncologica

    Barcelona, 08970

  • START - Hospital Universitario Madrid Sanchinarrio

    Madrid, 28050

  • Hospital Universitario Virgen del Rocio (HUVR)

    Seville, 41013

Other trials in Spain

About this study

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

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).

Being tested
Enadenotucirev
Medical subject headings
Colorectal Neoplasms, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnadenotucirevBiological

    Oncolytic virus

Study groups in NCT02028442
Study groupRoleWhat they receive
EnadenotucirevExperimentalNot described
Receives: Biological: Enadenotucirev

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to Day 22

  2. 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.

    Measured: Up to Day 134

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2014 (estimated)
  2. Study start20 Sep 2012
  3. Primary completion29 Apr 2016
  4. Study completion29 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02028442
Sponsor's protocol ID
ColoAd1-1001
Acronym
EVOLVE
Status last verified
Mar 2020
First submitted
29 Oct 2013
Last updated
12 Mar 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Khalil DN, Prieto Gonzalez-Albo I, Rosen L, Lillie T, Stacey A, Parfitt L, Soff GA. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023 Apr;41(2):317-323. doi: 10.1007/s10637-023-01345-8. Epub 2023 Mar 10.

    PubMed 36897458

  • 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.

    PubMed 30691536

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Enadenotucirev in people with Solid Tumours of Epithelial Origin and Metastatic Colorectal Cancer, run by Akamis Bio at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Belgium, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1 - Maximum Tolerated Dose (time frame: Up to Day 22). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02028442, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2020.

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