Endoscopic Assisted Calcium Electroporation in Esophageal Cancer

Endoscopic Assisted Calcium Electroporation in Esophageal Cancer - a Safety Study

In this pilot study, patients with non-curable esophageal cancer will be treated with endoscopic assisted calcium electroporation (CaEP). CaEP is a novel cancer treatment where intratumoral injection with calcium is combined with locally applied electrical pulses, in order to increase calcium influx which leads to tumor necrosis.

It is hypothesized that:

• Endoscopic assisted CaEP is a safe and feasible procedure in patients with non-curable esophageal cancer
• CaEP debulks the tumor, facilitating the patient's ability to eat and drink

In this single-arm pilot study, eight patients will be treated.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: Calcium Gluconate

Detailed Description

Electroporation facilitates the transport of molecules across the cell membrane and into the cell by means of electrical pulses. An electric field applied to the cell destabilizes the cell membrane forming cracks, which reseals after a few minutes. During this time slot, molecules which normally are impermeable to the cell membrane are able to cross into the cytosol of the cell. Within the last ten years, studies have shown that the combination of intratumoral injection of calcium and electroporation (Calcium electroporation/CaEP) is an effective method in killing cancer cells. CaEP has been evaluated in clinical studies in colorectal cancer, carcinomas in the head and neck area, and in cutaneous metastases with promising results.

In this single-arm pilot study, eight patients with non-curable esophageal cancer will be included.

It is hypothesized that:

• Endoscopic assisted CaEP is a safe and feasible procedure in patients with non-curable esophageal cancer
• CaEP debulks the tumor, facilitating the patient's ability to eat and drink
• CaEP induces a systemic immunological response

The primary objective is to evaluate the safety of CaEP for esophageal cancer. Adverse Events (AE) and Serious Adverse Events (SAE) will be evaluated.

Secondary outcomes include:

• dysphagia (Mellow Pinkas dysphagia score)
• pain (Numeric Rating Scale, NRS)
• quality of life (QoL) (EORTC QLQ-C30)
• tumor response evaluated from computed tomography (CT) and upper endoscopy
• immunologic response

Tertiary outcomes include:

✓ 90-days survival

Participants are initially treated once according to protocol. If well-tolerated, the treatment can be repeated.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥18 years old.
2. Histological verified malignant tumor in the esophagus.
3. Subjects must have been considered unsuitable for potential curative treatment.
4. Locally progressive disease, and other standard oncological treatment have been administrated and/or considered first.
5. Performance status ECOG/WHO < 2.
6. Expected survival > 3 months.
7. Platelets ≥ 50 billion/l, International Normalized Ratio (INR) < 1,5.
8. Subjects must be willing and able to comply with the procedure such as agreed follow-up visits.
9. Women of childbearing potential (WOCBP) and male partners to WOCBP should use adequate contraception during the trial.
10. Subjects must give written informed consent.

Exclusion Criteria:

1. Coagulation disorder that cannot be corrected.
2. Subjects with a clinically significant cardiac arrhythmia.
3. Pregnancy or lactation.
4. Concurrent treatment with another investigational medicinal product.
5. Stenosis that prevents passage of the endoscope with the device attached.
6. 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 requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calcium electroporation; Calcium gluconate 0.23 mmol/ml Maxium dosage 20 ml Intra tumoral injection	Drug: Calcium Gluconate; Calcium electroporation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Registration of all AE/SAE´s within the first 14 days after treatment. The events will be assessed by CTCAE v4.0.	14 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dysphagia	According to Mellow Pinkas dysphgia scale	After 7 days, 2-4 weeks and after 6-8 weeks.
Pain	Assesed by Numerical Rating Scale	After 7 days, 2-4 weeks and after 6-8 weeks.
Qualitiy of life	Assesed by "EORTC QLQ-C30"	After 7 days, 2-4 weeks and after 6-8 weeks.
90 days survival		90 days

Collaborators and Investigators

• Sponsor: Michael Patrick Achiam

Publications and helpful links

General Publications

• Egeland C, Baeksgaard L, Gehl J, Gogenur I, Achiam MP. Palliative Treatment of Esophageal Cancer Using Calcium Electroporation. Cancers (Basel). 2022 Oct 27;14(21):5283. doi: 10.3390/cancers14215283.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2021
• Primary Completion (Actual): June 13, 2022
• Study Completion (Actual): June 13, 2022

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: eCaEP2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No