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EMI-137 in Laparoscopic Colonic Resections

This study is currently recruiting participants.
Verified December 2017 by David Jayne, University of Leeds
Sponsor:
ClinicalTrials.gov Identifier:
NCT03360461
First Posted: December 4, 2017
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Edinburgh Molecular Imaging Ltd
Information provided by (Responsible Party):
David Jayne, University of Leeds
  Purpose

EMI-137 in laparoscopic colonic resections is a single-centre stage IIa developmental study.

Ten adult participants with a diagnosis of colon adenocarcinoma undergoing laparoscopic colonic will be recruited to the trial. Participants will receive a single intravenous dose of the IMP - EMI-137 1 to 3 hours before surgery. The ability of EMI-137 to produce visible intra-operative fluorescence of primary colon cancer and lymph node metastases will be explored and evaluated.


Condition Intervention Phase
Colonic Cancer Metastasis to Lymph Node Drug: EMI-137 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
Single-centre stage IIa developmental study, Open label, single arm, non-randomised feasibility study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intraoperative Imaging of Colon Cancer Using a Fluorescent Peptide (EMI-137) Against the c-Met Receptor

Further study details as provided by David Jayne, University of Leeds:

Primary Outcome Measures:
  • To investigate the ability of EMI-137 to produce visible fluorescence in regional lymph nodes draining the colon cancer. [ Time Frame: 6 months ]
    The ability of EMI-137 to detect colon cancer will be measured using the semi-quantitative descriptive terms of; highly fluorescent, mildly fluorescent and isofluorescent to background. The number of primary tumours highly or mildly fluorescent will be used to assess the success of EMI-137 as an imaging agent. The opinion of the senior operative surgeon performing the cases will also be taken in to consideration when appraising the efficacy of EMI-137.


Secondary Outcome Measures:
  • To investigate of the ability of EMI-137 to produce visible fluorescence in regional lymph nodes draining the colon cancer. [ Time Frame: 6 months ]
    The ability of EMI-137 to detect metastatic lymph nodes will be measured using the semi-quantitative descriptive terms of; highly fluorescent, mildly fluorescent and isofluorescent to background. The number of lymph nodes deemed to be highly or mildly fluorescent intraoperatively will be used to measure the success of EMI-137 as an imaging agent. The opinion of the senior operative surgeon performing the cases will also be taken in to consideration when appraising the efficacy of EMI-137.

  • To investigate the concordance of visible fluorescence in colon cancer with histological stage and c-MET expression in resected specimens. [ Time Frame: 6 months ]
    The resected specimen(s) will undergo thorough standard and trial-specific histopathological assessment. Cryosections will be taken from fresh frozen samples and analysed by fluorescent microscopy. The intraoperative fluorescence obtained will have been graded as either; highly fluorescent, mildly fluorescent or isofluorescent. The tumour stage will be ascertained and compared against the pre-operative radiological stage and the intraoperative fluorescence seen. High concordance will be a measure of success. The degree of fluorescence obtained may also be compared against the level of c-Met expression and the morphological and functional characteristics of the tumour. All comparisons will be made against the gold standard- standard histopathological assessment of the tumour, lymph nodes and the ascribed pathological stage of the tumour.

  • To investigate the concordance of visible fluorescence in cancer draining lymph nodes with histological evidence of metastasis. [ Time Frame: 6 months ]
    The pre-operative predicted lymph node status will be compared against the pathological lymph node status and the intra-operative lymph node appearance with the administration of EMI-137. Step sectioning and cytokeratin staining of fluorescent nodes will be performed if metastatic disease is not identified during standard histopathological analysis. High concordance between the intraoperative appearance and the final TMN lymph node status will be used as a measure of success.

  • To explore the tumour (signal) to background (noise) florescence [ Time Frame: 6 months ]
    The background (noise) appearance of nearby structures will be compared against the tumour and/lymph node (signal) in each case. High contrast between structures (high signal to noise ratio) will be used to measure the success of EMI-137 as an imaging agent. Factors likely to be negatively influencing the tumour to signal ratio will be evaluated and used to modify any further larger trials with EMI-137.

  • Investigation of the safety profile of EMI-137 [ Time Frame: 7 months ]
    The number of adverse events (AE/AR/SAE/SUSAR) arising from the administration of EMI-137 or the related surgery will be measured and reported.

  • Exploration of systemic, operative, and patient factors, which adversely affect EMI-137 fluorescence detection of colon cancer. [ Time Frame: 6 months ]
    Baseline demographic data will be analysed against the intraoperative and pathological results to determine any patient or surgical factors that negatively influence intra-operative visualisation with EMI-137. For example, Body Mass Index and tumour stage will be correlated to intraoperative results to determine possible adverse relationship.

  • Study of in vivo imaging compared against ex vivo fluorescent detection [ Time Frame: 6 months ]
    8. Fluorescent microscopy of fresh frozen biopsies from the resected specimen will be analysed for fluorescence. This will be compared and contrasted against the intra-operative appearance of the tumour and draining lymph nodes with EMI-137. The results will compared against the gold standard - histopathological assessment of tumour characteristics and TMN (tumour, node and metastases) stage for concordance. High concordance will be used to measure the success of EMI-137 as an imaging agent.


Estimated Enrollment: 10
Anticipated Study Start Date: December 21, 2017
Estimated Study Completion Date: July 21, 2018
Estimated Primary Completion Date: June 21, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EMI-137
Ten participants to receive the IMP - EMI-137 1 to 3 hours before laparoscopic colonic resection surgery. Dose range 0.02mg/kg to 0.13mg/kg will be administered.
Drug: EMI-137
EMI-137 - a fluorescent c-Met receptor targeted peptide

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • Patients with a diagnosis of colonic cancer (the disease can be of any radiological TMN stage and be located anywhere from the caecum up to but not including the rectosigmoid junction)
  • Patients with or without distant visceral or lymphatic metastatic disease.
  • Patients with synchronous colon cancers or polyps can participate.
  • American Society of Anaesthesiologists (ASA) classification ≤3.
  • Normal hepatic and renal function (eGFR ≥60 mls/min/1.73m2) and bilirubin within institutional limits and/or ALT ≤2.5x upper limit of institutional normal value) on serum laboratory blood tests performed ≤30 days prior to EMI-137 administration.
  • Female participants who are surgically sterile (documented bilateral oophorectomy and/or hysterectomy), post-menopausal (cessation of menses for more than 1 year), or pre-menopausal with two negative urine pregnancy tests performed within 24 hours of administration of EMI-137 Injection.
  • Pre-menopausal female participants of child-bearing potential who agree to employ two method of contraception (as defined in eligibility criteria of the protocol) during the study period and for 90 days after EMI-137 administration.
  • Male participants with a non-pregnant female partner. Male participants with a pre-menopausal partner of child-bearing potential who agree to use two forms of contraception (as defined in section 8.2) during the study period and for at least 90 days after receiving EMI-137. (The only permissible exception would be if the participant had undergone documented bilateral orchidectomy or their female partner is post-menopausal (cessation menses >1 year) or has undergone documented bilateral oophorectomy and/or hysterectomy).

Exclusion Criteria:

  • Patients who are participating in another intra-operative fluorescence study, or have participated in another fluorescence study within 3 months of the planned surgical procedure.
  • Received an investigational medicinal product at any dose within 28 days of planned EMI-137 administration
  • Patients with pre-existing inflammatory bowel disease.
  • Patients who have undergone neoadjuvant chemotherapy to treat the colon cancer.
  • Patients with impaired renal function (eGFR <60 mls/min/1.73m2).
  • Patients with impaired liver function (Bilirubin above institutional limits and/or ALT >2.5x upper limit of normal).
  • Pregnant and breastfeeding woman.
  • Pre-menopausal woman planning to become pregnant within 90 days of receiving EMI-137; or pre-menopausal woman of child-bearing potential who refuse to use two forms of contraception for at least 90 days after receiving EMI-137.
  • Male patients with a currently pregnant partner or male patients who are planning to conceive a pregnancy with a female partner within 90 days of receiving EMI-137; or male participants who refuse to use two forms of contraception as defined in section 8.2 for at least 90 days after receiving EMI-137 with their female partner of child-bearing potential.
  • Poorly controlled or serious medical or psychiatric illness that, in the investigator's opinion, is likely to interfere with participation and/or compliance in this clinical trial.
  • Previous adverse reaction to fluorescent agents.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03360461


Contacts
Contact: David G Jayne, MD 0113 206 5281 d.g.jayne@leeds.ac.uk
Contact: Gemma R Armstrong, MBChB 0113 343 1477 g.armstrong1@leeds.ac.uk

Locations
United Kingdom
St James' University Hospital Trust Recruiting
Leeds, United Kingdom, LS8 1RN
Contact: David G Jayne, MD    0113 206 5281    d.g.jayne@leeds.ac.uk   
Contact: Gemma R Armstrong, MBChB    0113 343 1477    g.armstrong1@leeds.ac.uk   
Sponsors and Collaborators
University of Leeds
Edinburgh Molecular Imaging Ltd
  More Information

Publications:
Responsible Party: David Jayne, Consultant Colorectal Surgeon, University of Leeds
ClinicalTrials.gov Identifier: NCT03360461     History of Changes
Other Study ID Numbers: GS16/87090
First Submitted: November 7, 2017
First Posted: December 4, 2017
Last Update Posted: December 7, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases