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Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer (nECT)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03040180
Recruitment Status : Unknown
Verified January 2019 by Zealand University Hospital.
Recruitment status was:  Recruiting
First Posted : February 2, 2017
Last Update Posted : January 25, 2019
Sponsor:
Collaborators:
Herlev Hospital
Rigshospitalet, Denmark
Information provided by (Responsible Party):
Zealand University Hospital

Tracking Information
First Submitted Date  ICMJE January 25, 2017
First Posted Date  ICMJE February 2, 2017
Last Update Posted Date January 25, 2019
Actual Study Start Date  ICMJE January 2017
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
Histopathologic tumor regression following electrochemotherapy [ Time Frame: 4 weeks ]
Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
  • Treatment safety of electrochemotherapy [ Time Frame: 4 months ]
    Number of participants with treatment-related adverse events as assesed by CTCAE version 4.0
  • Treatment safety of surgery following electrochemotherapy [ Time Frame: 4 weeks ]
    Number of participants with compromized surgery following electrochemotherapy assesed by R1 resection rate, CRM involvement, non-mesorectal resection plane, and post operative complications according to Clavien-Dindo Classification
  • Tumor regression according to Hybrid PET/MRI following electrochemotherapy [ Time Frame: 4 weeks ]
    Tumor regression as assesed by tumor stage (T-stage)
  • Tumor Immunologic response following electrochemotherapy [ Time Frame: 4 weeks ]
    Tumor immunologic infiltration as assesed by the Immunoscore through immunohistochemical analysis
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer
Official Title  ICMJE Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial
Brief Summary The purpose of this study is to evaluate the efficacy and safety of neoadjuvant electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative clinical setting, using an endoscopic electroporation device (EndoVE).
Detailed Description

Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy or ECT). The pulses make the tumor cells more porous which allows the drug easier access into the cancer cells, whereas other tissues and organs in the body remain relatively poor at absorbing the drug, thereby reducing the potential side effects on healthy tissues. Procedures with electrochemotherapy have previously been applied to human patients in other countries of the EU, the US and Japan.

The drug concentration used is significantly reduced due to the more targeted absorption by the tumor and this significantly reduces side effects normally associated with chemotherapy.

A large number of preclinical and clinical Phase I and I/II studies have demonstrated the efficiency and safety of ECT. These studies have included patients with melanoma, head and neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma nodules.

An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors has recently been developed. The treatment procedure is similar to standard endoscopic colorectal examination (therapeutic colonoscopy) with the added element of an intravenous injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire procedure is minimally invasive and completely ambulatory. A successful treatment will cause the tumor to shrink in size in the weeks following the procedure.

The objective of this study is to investigate the efficacy and safety of this approach in downsizing locally advanced rectal tumors prior to intended curative surgery.

Time frame:

  1. All patients will be treated with standard neoadjuvant chemoradiation therapy prior to enrollment in this trial.
  2. Alle patients will have PET/MRI scans performed twice to evaluate treatment response (before and after ECT)
  3. ECT treatment will be performed 4 weeks prior to surgery outlined by MDT.
  4. Alle patients will be followed up for 3 months.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Locally Advanced Rectal Cancer
  • Electrochemotherapy
  • Neoadjuvant Therapy
  • Down Staging
Intervention  ICMJE
  • Drug: Electrochemotherapy with bleomycin
    Systemic injection, once only treatment
    Other Names:
    • ATC code L01DC01
    • EV substance code SUB00844MIG
  • Device: EndoVE
    Electroporation using an endoscopic electroporation device
    Other Name: Endoscopic electroporation
Study Arms  ICMJE
  • Experimental: Electrochemotherapy with bleomycin

    Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.

    BSA by Du Bois formula.

    Interventions:
    • Drug: Electrochemotherapy with bleomycin
    • Device: EndoVE
  • No Intervention: Standard care
    Standard care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 30, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient must be mentally capable of understanding the information given.
  2. Patients must give written informed consent.
  3. Men or women aged at least 18 years.
  4. Histologically verified rectal tumor (adenocarcinoma)
  5. Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with neoadjuvant therapy followed by surgical excision (UICC stadium II-III).
  6. ASA class I-III (Classification of the American Society of Anesthesiology)

Exclusion Criteria:

  1. Coagulation disorders
  2. Highly inflamed gastrointestinal tissue which is ulcerated and bleeding
  3. Patients with ICD or pacemaker units.
  4. Patients with epilepsy.
  5. Pregnancy or lactation/breastfeeding.
  6. Patients with known Hepatitis B/C or HIV infection.
  7. Patients who have undergone treatment with bevacizumab within 4 weeks prior to enrolment in this trial.
  8. Patients with concomitant use of phenytoin.
  9. Patients with concomitant use of clozapine.
  10. Concurrent treatment with an investigational medicinal product.
  11. Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study recruitments.
  12. Patients with contraindications for PET/MRI scan:
  13. Advanced tumor stage, UICC stage IV.
  14. Acute pulmonary infection.
  15. Medical history of severe pulmonary disease.
  16. Previous allergic reactions to bleomycin.
  17. Previous cumulative dose of bleomycin exceeding 250.000 IU/m2.
  18. Pre-existing renal dysfunction. Creatinine clearance < 40 ml/min.
  19. Platelet count ≤50 mia/l.
  20. Prothrombin time ≥ 40 sec
  21. Patients registered in the Danish Tissue Register (Vaevsanvendelsesregistret)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03040180
Other Study ID Numbers  ICMJE REG-32-2016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Undecided
Responsible Party Zealand University Hospital
Study Sponsor  ICMJE Zealand University Hospital
Collaborators  ICMJE
  • Herlev Hospital
  • Rigshospitalet, Denmark
Investigators  ICMJE
Principal Investigator: Ismail Gögenur, Professor Department of Surgery, Zealand University Hospital
Principal Investigator: Julie Gehl, MD, DMSc Department of oncology, herlev Hospital
PRS Account Zealand University Hospital
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP