Trial Outcomes & Findings for Confirmatory Trial in the Evaluation of Ca Electroporation for the Treatment of Cutaneous Metastases (NCT NCT03628417)
NCT ID: NCT03628417
Last Updated: 2020-01-02
Results Overview
Documentation was done with digital color photography, including a ruler to estimate tumor size. Primary evaluation of the response was based on criteria similar RECIST 1.1 guidelines and defined as complete response (CR) - disappearance of the lesion, partial response (PR) - at least 30% decrease in the largest diameter of the lesion, progressive disease - at least 20% increase in the largest diameter of the lesion and stable disease - neither 30% decrease nor 20% increase of the largest diameter of the lesion. Change in the largest diameter:
COMPLETED
NA
7 participants
180 days after treatment
2020-01-02
Participant Flow
Participants with cutan metastases of melanoma malignum and breast cancer were followed-up at one of the academic medical center in Hungary between September 2016 and June 2019 based on oncologist refferal.
Enrolled participants were not excluded from the study before assignment to groups. Block randomization was performed separately on each metastasis, so the patients received both treatments. The bleomycin and calcium syringes were mixed and labeled with numbers according to the metastases.
Unit of analysis: cutan metastases
Participant milestones
| Measure |
Calcium Electroporation
Volume of calcium chloride (220 mmol/L) was dependent on tumor volume. Smaller tumors should have bigger volume per cm³, as smaller tumors were expected to have a bigger loss of injected medicine into the surrounding tissue.The dose volume was calculated according to the 'European Standard Operating Procedure of the Electrochemotherapy'.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a") Biopsies were performed from the tumor area before and after electroporation. Maximum of 8 biopsies were done, depending on the patient's number of metastases. All patient's regardless of the number of metastases had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code was revealed at day 180.
All biopsies were handled and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
Bleomycin Based Electrochemotherapy
Both dose and volume of bleomycin (1000 IU/ml) was standard according to ESOPE.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a") Maximum of injected bleomycin per tumor was 1500 IU and total dose per treatment was 7500 IU.
Biopsies were performed from the tumor area before and after electroporation. Maximum of 8 biopsies were done, depending on the patient's number of metastases. All patient's regardless of the number of metastases had one biopsy from area treated with bleomycin and one from area treated with calcium, after the randomization code was revealed at day 180.
All biopsies will be handled according to current guidelines and analyzed by a pathologist.
|
|---|---|---|
|
Overall Study
STARTED
|
7 24
|
7 20
|
|
Overall Study
Day 0
|
7 21
|
7 17
|
|
Overall Study
Day 7
|
7 18
|
7 15
|
|
Overall Study
Day 15
|
7 18
|
7 15
|
|
Overall Study
Day 30
|
7 18
|
7 15
|
|
Overall Study
Day 60
|
7 18
|
7 15
|
|
Overall Study
Day 90
|
7 18
|
7 15
|
|
Overall Study
Day 180
|
7 12
|
7 9
|
|
Overall Study
COMPLETED
|
6 7
|
6 7
|
|
Overall Study
NOT COMPLETED
|
1 17
|
1 13
|
Reasons for withdrawal
| Measure |
Calcium Electroporation
Volume of calcium chloride (220 mmol/L) was dependent on tumor volume. Smaller tumors should have bigger volume per cm³, as smaller tumors were expected to have a bigger loss of injected medicine into the surrounding tissue.The dose volume was calculated according to the 'European Standard Operating Procedure of the Electrochemotherapy'.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a") Biopsies were performed from the tumor area before and after electroporation. Maximum of 8 biopsies were done, depending on the patient's number of metastases. All patient's regardless of the number of metastases had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code was revealed at day 180.
All biopsies were handled and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
Bleomycin Based Electrochemotherapy
Both dose and volume of bleomycin (1000 IU/ml) was standard according to ESOPE.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a") Maximum of injected bleomycin per tumor was 1500 IU and total dose per treatment was 7500 IU.
Biopsies were performed from the tumor area before and after electroporation. Maximum of 8 biopsies were done, depending on the patient's number of metastases. All patient's regardless of the number of metastases had one biopsy from area treated with bleomycin and one from area treated with calcium, after the randomization code was revealed at day 180.
All biopsies will be handled according to current guidelines and analyzed by a pathologist.
|
|---|---|---|
|
Overall Study
Death
|
1
|
1
|
Baseline Characteristics
Confirmatory Trial in the Evaluation of Ca Electroporation for the Treatment of Cutaneous Metastases
Baseline characteristics by cohort
| Measure |
All Study Participants
n=7 Participants
All participants receiving Calcium Electroporation and Bleomycin Based Electrochemotherapy.
|
|---|---|
|
Age, Customized
Age
|
70 years
n=39 Participants
|
|
Sex/Gender, Customized
Female
|
5 Participants
n=39 Participants
|
|
Sex/Gender, Customized
Male
|
2 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
7 Participants
n=39 Participants
|
|
Patients with cutaneous metastases
Patients with MM cutaneous metastases
|
6 Participants
n=39 Participants
|
|
Patients with cutaneous metastases
Patients with breast cc. cutaneous metastases
|
1 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: 180 days after treatmentPopulation: There were 7 patients with a total of 44 cutaneous metastases which were randomized. We chose up to 10 tumours on each patient. At the first 6 tumours we examined the clinical response rate, and (if they had more) the rest 4 were used for biopsy. 33 from the 44 lesions were evaluated in clinical response, the rest were used for biopsy.
Documentation was done with digital color photography, including a ruler to estimate tumor size. Primary evaluation of the response was based on criteria similar RECIST 1.1 guidelines and defined as complete response (CR) - disappearance of the lesion, partial response (PR) - at least 30% decrease in the largest diameter of the lesion, progressive disease - at least 20% increase in the largest diameter of the lesion and stable disease - neither 30% decrease nor 20% increase of the largest diameter of the lesion. Change in the largest diameter:
Outcome measures
| Measure |
Calcium Electroporation
n=18 cutaneous metastases
Volume of calcium chloride (220 mmol/L) was dependent on the tumor volume. Smaller tumors should have bigger volume per cm3, as smaller tumors were expected to have a bigger loss of injected medicine into the surrounding tissue. The dose volume was calculated according to the 'European Standard Operating Procedure of the Electrochemotherapi (ESOPE)'.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")
All patient's regardless of the number of metastases have had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180.
All biopsies were handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
Bleomycin Based Electrochemotherapy
n=15 cutaneous metastases
Both dose and volume of bleomycin (1000 IU/ml) is standard according to ESOPE.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")
Maximum of injected bleomycin per tumor was1500 IU and total dose per treatment 7500 IU. Normal maximum limit for bleomycin was 15.000 IU/m² body surface area.
All patient's regardless of the number of metastases have had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180.
All biopsies were handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
|---|---|---|
|
Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.
PR
|
2 cutaneous metastases
|
2 cutaneous metastases
|
|
Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.
SD
|
6 cutaneous metastases
|
5 cutaneous metastases
|
|
Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.
CR
|
4 cutaneous metastases
|
6 cutaneous metastases
|
|
Response Rate (RECIST1.1) of Calcium Electroporation and Bleomycin Based Electrochemotherapy on Cutaneous Metastases at Day 180.
PD
|
6 cutaneous metastases
|
2 cutaneous metastases
|
SECONDARY outcome
Timeframe: 180 days after treatment* Adverse Event, AE: Any adverse events in a patient that occur or worsen during the trial and does not necessarily have a causal relationship to study treatment * Adverse Reaction, AR: All noxious and unintended reactions to a trial drug at any dose (possible relation between the study drug and the adverse reaction cannot be excluded) * Unexpected Adverse Reaction, UAR: An adverse reaction with a nature or severity that is not in accordance with the current product information (Investigator's Brochure) * Serious Adverse Event, SAE: an event or side effect that at any dose: * Results in death * Is life threatening * Leads to hospitalization or prolongation of hospital stay * Results in persistent or significant disability or incapacity * Leads to a congenital anomaly or birth defect * Is a major medical event * Suspected Unexpected Serious Adverse Reactions, SUSARs: adverse reactions that are not described in the product information for the experimental drug
Outcome measures
| Measure |
Calcium Electroporation
n=18 cutaneous metastases
Volume of calcium chloride (220 mmol/L) was dependent on the tumor volume. Smaller tumors should have bigger volume per cm3, as smaller tumors were expected to have a bigger loss of injected medicine into the surrounding tissue. The dose volume was calculated according to the 'European Standard Operating Procedure of the Electrochemotherapi (ESOPE)'.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")
All patient's regardless of the number of metastases have had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180.
All biopsies were handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
Bleomycin Based Electrochemotherapy
n=15 cutaneous metastases
Both dose and volume of bleomycin (1000 IU/ml) is standard according to ESOPE.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")
Maximum of injected bleomycin per tumor was1500 IU and total dose per treatment 7500 IU. Normal maximum limit for bleomycin was 15.000 IU/m² body surface area.
All patient's regardless of the number of metastases have had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180.
All biopsies were handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
|---|---|---|
|
Adverse Events for Calcium Electroporation and Bleomycin Based Electrochemotherapy. The Adverse Reactions Are Classified According to CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).
Itch
|
0 cutaneous metastases
|
0 cutaneous metastases
|
|
Adverse Events for Calcium Electroporation and Bleomycin Based Electrochemotherapy. The Adverse Reactions Are Classified According to CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).
Ulceration
|
2 cutaneous metastases
|
3 cutaneous metastases
|
|
Adverse Events for Calcium Electroporation and Bleomycin Based Electrochemotherapy. The Adverse Reactions Are Classified According to CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).
Hyperpigmentation
|
2 cutaneous metastases
|
6 cutaneous metastases
|
|
Adverse Events for Calcium Electroporation and Bleomycin Based Electrochemotherapy. The Adverse Reactions Are Classified According to CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events).
Flu-like symptoms
|
0 cutaneous metastases
|
0 cutaneous metastases
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 - During Ca-electroporation and bleomycin based electrochemotherapy interventionsWe measured the maximum electric current which was given to the metastases. The measurement was needed because the current is unknown during Ca-electroporation, and also we would like to determine wether there is a difference between bleomycin based electrochemotherapy and calcium electroporation in current.
Outcome measures
| Measure |
Calcium Electroporation
n=18 cutaneous metastases
Volume of calcium chloride (220 mmol/L) was dependent on the tumor volume. Smaller tumors should have bigger volume per cm3, as smaller tumors were expected to have a bigger loss of injected medicine into the surrounding tissue. The dose volume was calculated according to the 'European Standard Operating Procedure of the Electrochemotherapi (ESOPE)'.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")
All patient's regardless of the number of metastases have had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180.
All biopsies were handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
Bleomycin Based Electrochemotherapy
n=15 cutaneous metastases
Both dose and volume of bleomycin (1000 IU/ml) is standard according to ESOPE.
* Tumor \< 0.5 cm³ - 1 ml/cm³ tumor volume
* Tumor \> 0.5 cm³ - 0,5 ml/cm³ tumor volume Tumor volume = ab²π/6 (a = longest diameter, b = longest diameter perpendicular to "a")
Maximum of injected bleomycin per tumor was1500 IU and total dose per treatment 7500 IU. Normal maximum limit for bleomycin was 15.000 IU/m² body surface area.
All patient's regardless of the number of metastases have had one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180.
All biopsies were handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.
|
|---|---|---|
|
The Tertiary Outcome is to Register if Calcium Affects the Current Strength in Electroporation Treatments.
|
3.850 Amper
Interval 1.4 to 9.0
|
4.000 Amper
Interval 1.4 to 6.5
|
Adverse Events
Calcium Electroporation
Bleomycin Based Electrochemotherapy
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Calcium Electroporation
n=7 participants at risk
Experiences from treating small tumors with electrochemotherapy, show that the treated area initially can become erythmatose and swollen, but this fades quickly. The area can then become necrotic which heals within 6-10 weeks. In a few cases, infection may occur in the treatment area. With calcium electroporation we expect to see the same response to treatment.
|
Bleomycin Based Electrochemotherapy
n=7 participants at risk
At electrochemotherapy the most reported adverse events are pain after the procedure and flu-like symptoms. The latter is a reaction to bleomycin and is therefore not expected by calcium electroporation.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Other primary tumor
|
14.3%
1/7 • Number of events 1 • 180 days after treatment
Any adverse events in a patient that occur or worsen during the trial and does not necessarily have a causal relationship to study treatment
|
14.3%
1/7 • Number of events 1 • 180 days after treatment
Any adverse events in a patient that occur or worsen during the trial and does not necessarily have a causal relationship to study treatment
|
Additional Information
Principal Investigator, Assistant Professor
Szeged University
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place