Title

CEDAR

Chief Investigator: 

 

 

 

FULL TITLE

A Phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer

Sponsor: University of Oxford

STUDY DESIGN

CEDAR is a dual endpoint dose escalation phase I trial. Response and Toxicity endpoints will be combined in dose escalation models to identify the optimal dose schedule.

STUDY POPULATION

Patients with histologically confirmed invasive adenocarcinoma of the Rectum.

STUDY STATUS

STUDY STATUS

Opening soon

TARGET RECRUITMENT

30 Patients Total

CURRENT RECRUITMENT

None (As of Jun2018)

PARTICIPATING SITE

Churchill Hospital – Oxford University Hospital Trust

STUDY FLOW CHART

INCLUSION CRITERIA

A patient will be eligible for inclusion in this trial if all of the following criteria apply.

  • Histologically confirmed invasive adenocarcinoma of the rectum.
  • Locally advance colorectal cancer as defined by pelvic MRI  with a threatened circumferential resection margin (cT3mrf+ve), or inclusion of an adjacent organ, or low tumours at/below the level of the levators or enlarged pelvic side wall nodes  or selected by the multidisciplinary team MDT for treatment with neoadjuvant (chemo)radiotherapy, regardless of TNM classification
  • Patients with oligometastatic disease suitable for radical treatment
  • Male or female, Age ³ 18 years.
  • ECOG performance score of 0 - 1
  • The patient is willing and able to comply with the protocol scheduled biopsy, follow-up visits and examinations for the duration of the trial.
  • Written (signed and dated) informed consent.
  • Adequate renal function demonstrated by:
    • Creatinine ≤1.5 mg/dL and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2 (or measured creatinine clearance ≥60 mL/min) AND
    • 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:
      • ≤3 mg/mmol OR

      • >3 mg‑<70 mg/mmol with a 24 hour urinary protein <0.2 g/24hours AND

      • Serum complement components C3 and C4 within the normal range
  • Haematological and biochemical indices within the ranges shown below:

Lab Test

Value required

Haemoglobin (Hb)

≥90 g/L

White Blood Count (WBC)

absolute neutrophil count ≥1.5x109/L

Platelet count

≥100x109/L

Bilirubin

< 1.5 mg/dL

Aspartate transaminase and/or alanine transaminase

≤3xupper limit of normal

INR

≤1.5

EXCLUSION CRITERIA

A patient will not be eligible for the trial if any of the following apply:

  • Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
  • Past medical history:
    • Known history or evidence of significant immunodeficiency due to underlying illness and/or medication (e.g. systemic corticosteroids, or other immunosuppressive medications including cyclosporine, azathioprine, interferons in the 4 weeks before the first dose of trial treatment)
    • Splenectomy
    • Prior allogeneic or autologous bone marrow or organ transplantation
    • Patients with a history of, or 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
    • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or evidence of active pneumonia or pneumonitis on computed tomography scan
    • Active viral disease or known positive serology for HIV, hepatitis B or hepatitis C
    • Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0˚C associated with a clinical diagnosis of active infection
    • Prior pelvic radiotherapy
    • Any other active malignancy
    • Uncontrolled cardiorespiratory comorbidity (e.g. inadequately controlled angina or myocardial infarction in the last 6 months)
    • Major disturbance in bowel function ( e.g severe incontinence, Crohn’s disease, >6 loperamide/day)
  • Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to the first dose of trial treatment; or pegylated interferon in the 14 days before the first dose of trial treatment
  • Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment. Observational studies are allowed
  • Warfarin that cannot be discontinued at least 7 days prior to starting treatment
  • Known dihydropyrimidine dehydrogenase (DPYD) deficiency.
  • Prior chemotherapy is allowed as long as >28 days since the last administration and any toxicity has resolved to NCI CTCAE grade 1 or less
  • Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.

PRIMARY OBJECTIVE

  • Determine the optimal dose and frequency of enadenotucirev that can be administered with chemoradiation.

SECONDARY OBJECTIVES

  • Ability to deliver enadenotucirev concurrently with chemoradiation.
  • To measure local response rate to combined therapy compared to pre-treatment status.

KEY DATES

Open to recruitment: Await Opening

End of Recruitment: May 2021

End of Trial: March 2022

 

DATA SUBMISSION

Data submission for this trial is via electronic submission of data in OpenClinica.

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