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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03040180
Recruitment Status : 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

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).

Condition or disease Intervention/treatment Phase
Locally Advanced Rectal Cancer Electrochemotherapy Neoadjuvant Therapy Down Staging Drug: Electrochemotherapy with bleomycin Device: EndoVE Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial
Actual Study Start Date : January 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy

Arm Intervention/treatment
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.

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

No Intervention: Standard care
Standard care



Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Treatment safety of electrochemotherapy [ Time Frame: 4 months ]
    Number of participants with treatment-related adverse events as assesed by CTCAE version 4.0

  2. 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

  3. Tumor regression according to Hybrid PET/MRI following electrochemotherapy [ Time Frame: 4 weeks ]
    Tumor regression as assesed by tumor stage (T-stage)

  4. Tumor Immunologic response following electrochemotherapy [ Time Frame: 4 weeks ]
    Tumor immunologic infiltration as assesed by the Immunoscore through immunohistochemical analysis



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT03040180


Contacts
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Contact: Ismail Gögenur, MD, DMSc +45 26336426 igo@regionsjaelland.dk
Contact: Rasmus P Vogelsang, MD +45 27351103 rvo@regionsjaelland.dk

Locations
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Denmark
Department of Oncology Recruiting
Herlev, Capitol Region, Denmark, 2730
Contact: Julie Gehl, MD, DMSc    +45 38683868    karen.julie.gehl@regionh.dk   
Department of Surgery Recruiting
Roskilde, Denmark, 4000
Contact: Ismail Gögenur, MD, DMSc    +45 26336426    igo@regionsjaelland.dk   
Contact: Rasmus P Vogelsang, MD    +45 27351103      
Sponsors and Collaborators
Zealand University Hospital
Herlev Hospital
Rigshospitalet, Denmark
Investigators
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Principal Investigator: Ismail Gögenur, Professor Department of Surgery, Zealand University Hospital
Principal Investigator: Julie Gehl, MD, DMSc Department of oncology, herlev Hospital
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Responsible Party: Zealand University Hospital
ClinicalTrials.gov Identifier: NCT03040180    
Other Study ID Numbers: REG-32-2016
First Posted: February 2, 2017    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided
Keywords provided by Zealand University Hospital:
Neoplasms
Neoplasms, primary
Cancer
Colorectal cancer
rectal cancer
rectal cancer, locally advanced
Electrochemotherapy
Electroporation
Neoadjuvant therapy
Antineoplastic, antibodies
Bleomycin
Pathologic processes
Neoplastic processes
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Bleomycin
Antibiotics, Antineoplastic
Antineoplastic Agents