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Full Title

CEDARA 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

Chief Investigator: Maria Hawkins

Sponsor: University of Oxford

 

 

 

Contact Us

CEDAR Trial Office

Email: octo-CEDAR@oncology.ox.ac.uk

 

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

Open for recruitment

TARGET RECRUITMENT

30 Patients Total

CURRENT RECRUITMENT

2 patients (As of Feb2020)

PARTICIPATING SITE

Churchill Hospital – Oxford University Hospital Trust

 

Study Flow Chart

CEDAR Flowchart

 

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

  1. Histologically confirmed invasive adenocarcinoma of the rectum.
  2. 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
  3. Patients with oligometastatic disease suitable for radical treatment are permitted provided that the site specific MDT deems them suitable for chemoradiation
  4. Male or female, Age ³ 18 years.
  5. ECOG performance score of 0 - 1
  6. The patient is willing and able to comply with the protocol scheduled biopsy, follow-up visits and examinations for the duration of the trial.
  7. Written (signed and dated) informed consent.
  8. Adequate renal function demonstrated by:

Creatinine ≤1.5 ULN 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:

(i) ≤3 mg/mmol or

(ii) >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

 9.     Haematological and biochemical indices within the ranges shown below:

Lab Test

Value required

Haemoglobin (Hb)

≥90 g/L

Absolute neutrophil count

 ≥1.5x109/L

Platelet count

≥100x109/L

Bilirubin

< 1.5 upper limit of normal

Aspartate transaminase and/or alanine transaminase

≤3 x upper limit of normal

INR

≤1.5

aPTT

Within laboratory normal range

 

EXCLUSION CRITERIA

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

  1. Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used.
  1. Pulmonary lymphangitis  (if metastatic disease present)
  2. Past medical history:
    1. 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)
    2. Splenectomy
    3. Prior allogeneic or autologous bone marrow or organ transplantation
    4. 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
    5. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or evidence of active pneumonia or pneumonitis on computed tomography scan
    6. Active viral disease or known positive serology for HIV, hepatitis B or hepatitis C
    7. Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0˚C associated with a clinical diagnosis of active infection
    8. Prior pelvic radiotherapy
    9. Any other active malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions.
    10. Uncontrolled cardiorespiratory comorbidity (e.g. severe pulmonary fibrosis,  inadequately controlled angina or myocardial infarction in the last 6 months)
    11. Major disturbance in bowel function ( e.g. severe incontinence, Crohn’s disease, >6 loperamide/day), risk of bowel obstruction due to tumour- exception defunctioning colostomy performed
  1. 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
  2. Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment. In follow up for an interventional trials and observational studies are allowed
  3. History of DVT or pulmonary embolus in the 12 months before the first dose of study treatment
  4. History of significant bleeding requiring hospitalisation in the 12 months before the first dose of study treatment
  5. Patients receiving therapeutic or prophylactic anticoagulation therapy
  6. Known dihydropyrimidine dehydrogenase (DPYD) deficiency
  7. 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
  8. 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: July 2019

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. 

 

Contact Us

CEDAR Trial Office

Tel: +44 (0)1865 617087

Email: octo-CEDAR@oncology.ox.ac.uk

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