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

• ClinicalTrials.gov Identifier: NCT03040180
• Recruitment Status: Unknown
• First Posted: February 2, 2017
• Last Update Posted: January 25, 2019
• Sponsor: Zealand University Hospital
• Collaborators: Herlev Hospital; Rigshospitalet, Denmark
• Information provided by (Responsible Party): Zealand University Hospital

Tracking Information

• First Submitted Date: January 25, 2017
• First Posted Date: February 2, 2017
• Last Update Posted Date: January 25, 2019
• Actual Study Start Date: January 2017
• Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Locally Advanced Rectal Cancer
• Electrochemotherapy
• Neoadjuvant Therapy
• Down Staging

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 30, 2017): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2019
• Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT03040180
• Other Study ID Numbers: REG-32-2016
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: Undecided

• Responsible Party: Zealand University Hospital
• Study Sponsor: Zealand University Hospital

Collaborators

• Herlev Hospital
• Rigshospitalet, Denmark

Investigators

• 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