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Irradiation of Melanoma in a Pulse (IMPulse)

Primary Purpose

Metastasis From Malignant Melanoma of Skin (Diagnosis)

Status

Recruiting

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

FLASH therapy

About this trial

This is an interventional treatment trial for Metastasis From Malignant Melanoma of Skin (Diagnosis) focused on measuring FLASH therapy, melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed study Informed Consent Form
Karnofsky Performance Status (KPS) ≥ 50
Age ≥ 18 years
Patients with metastatic melanoma and multiple skin metastases with a documented clinical progression despite the systemic treatments (chemotherapy, and/or Programmed cell death 1 (PD1), cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors or tyrosine kinase inhibitors (TKIs), such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) or mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors)
The size of the treated lesions should be ≤ 5.5 cm in diameter and ≤ 2.8 cm thick (caliper-based measurement)
The treated lesions should be at least 5 cm apart and must not be located on the face.
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine or serum) during screening
WOCBP must use a contraceptive method

Exclusion Criteria:

Previous radiotherapy in the treated area
Concomitant auto-immune disease with skin lesions
Concomitant use of radio-sensitizer drug
Women who are pregnant
Current, recent (within 10 days prior start of study treatment), or planned participation in an experimental drug study. During the 4 weeks DLT period, the patient will not be able to participate to any other clinical study.
Any serious underlying medical condition that could interfere with study treatment and potential adverse events
Any mental or other impairment that may compromise compliance with the requirements of the study

Sites / Locations

Centre Hospitalier Universitaire Vaudois (CHUV)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc)

Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc)

Arm Description

7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy)

Outcomes

Primary Outcome Measures

Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes.

Acute safety (dose limiting toxicity, DLT) of the high dose rate radiotherapy (RT) procedure (for each dose level) will be evaluated during the 4 weeks post-treatment using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Secondary Outcome Measures

Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator

Hemorrhage will be visually assessed (presence/abscence)

Percentage of patients with Skin ulceration related to the treated lesions, assessed visually by the investigator

Skin ulceration will be visually assessed (presence/abscence)

Percentage of patients with Pain related to the treated lesions, assessed with analogic visual pain scale

Pain will be assessed using an analogic visual pain scale (score from 1 to 10)

Local response of metastases "in the radiation field", measured with calipers

Irradiated lesions will be measured with calipers. Local response of metastases in the radiation field will be calculated as rate over all treated lesions and will be compared between small versus large volume lesions within each dose level.

Frequency of Late side effects observed "in radiation field"

Blinded Imaging Central Review (BICR) of photographs evaluating both tumor response and "in radiation field" normal tissue responses around the treated tumors

A baseline photograph will be taken the day of the treatment in a pre-therapeutic setting with skin delineation of the lesion. Then photos will be repeated at 1 (+/-2d), 3 (+/-2d), 4 (+/-3d), 6 (+/-3d) weeks after treatment, then at 3 (+/-7d), 6 (+/-14d), 12 (+/-14d) months and at progression.

Optical coherence tomography (OCT) examination of the irradiated skin compared to the normal non-irradiated skin

Epidermis thickness and roughness; plexus depth; number and size of vessels; number and size of hairs, will be compared between irradiated skin and normal non-irradiated skin

Frequency of late adverse events (within 12 months post-treatment) for each dose

Long-term safety of RT procedure will be measured as recording of late adverse events (CTCAE v5.0)

Full Information

NCT ID

NCT04986696

First Posted

July 2, 2021

Last Updated

September 19, 2023

Sponsor

Centre Hospitalier Universitaire Vaudois

1. Study Identification

Unique Protocol Identification Number

NCT04986696

Brief Title

Irradiation of Melanoma in a Pulse

Acronym

IMPulse

Official Title

A Phase I, First-in-human, Dose Finding Study of High Dose Rate Radiotherapy in Patients With Skin Metastases From Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 1, 2021 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centre Hospitalier Universitaire Vaudois

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a single center phase I, first-in-human, dose escalation study of FLASH therapy in patients with metastases of melanoma. The trial is based on escalating single doses of FLASH therapy administered to skin melanoma metastases using the Mobetron® with high dose rate (HDR) functionality. The aim of the study is to evaluate a dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments. Melanoma is a typically radio-resistant tumor type, which can justify such a dose escalation with a new type of radiotherapy that appears much better tolerated than conventional radiotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastasis From Malignant Melanoma of Skin (Diagnosis)

Keywords

FLASH therapy, melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Sequential Assignment

Model Description

Dose escalation study

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc)

Arm Type

Experimental

Arm Description

7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy)

Arm Title

Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc)

Arm Type

Experimental

Arm Description

7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy)

Intervention Type

Device

Intervention Name(s)

FLASH therapy

Other Intervention Name(s)

high dose rate radiotherapy

Intervention Description

Dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments.

Primary Outcome Measure Information:

Title

Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes.

Description

Time Frame

from Day 1 to Day 28

Secondary Outcome Measure Information:

Title

Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator

Description

Hemorrhage will be visually assessed (presence/abscence)

Time Frame

At each visit, from screening to 12 months post-treatment

Title

Percentage of patients with Skin ulceration related to the treated lesions, assessed visually by the investigator

Description

Skin ulceration will be visually assessed (presence/abscence)

Time Frame

At each visit, from screening to 12 months post-treatment

Title

Percentage of patients with Pain related to the treated lesions, assessed with analogic visual pain scale

Description

Pain will be assessed using an analogic visual pain scale (score from 1 to 10)

Time Frame

At each visit, from screening to 12 months post-treatment

Title

Local response of metastases "in the radiation field", measured with calipers

Description

Time Frame

At screening, Day 1, at weeks 1, 3, 4, and 6 post-treatment; at months 3, 6, and 12 post-treatment; and at local progression

Title

Frequency of Late side effects observed "in radiation field"

Time Frame

≥ 6 months post-treatment

Title

Blinded Imaging Central Review (BICR) of photographs evaluating both tumor response and "in radiation field" normal tissue responses around the treated tumors

Description

Time Frame

From Day 1 up to 12 months post-treatment

Title

Optical coherence tomography (OCT) examination of the irradiated skin compared to the normal non-irradiated skin

Description

Epidermis thickness and roughness; plexus depth; number and size of vessels; number and size of hairs, will be compared between irradiated skin and normal non-irradiated skin

Time Frame

at 4 weeks, 6 months and 12 months post-treatment

Title

Frequency of late adverse events (within 12 months post-treatment) for each dose

Description

Long-term safety of RT procedure will be measured as recording of late adverse events (CTCAE v5.0)

Time Frame

within 12 months post-treatment

Other Pre-specified Outcome Measures:

Title

Observation of a potential Abscopal Effect with evidence of tumor regression on metastases outside of the radiation field, measured with a caliper for cutaneous lesion or on radiological images for other lesions

Description

Time Frame

within 12 months post-treatment (at 1, 3, 4, 6 weeks post-treatment; at 3, 6, 12 months post-treatment; at progression)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed study Informed Consent Form Karnofsky Performance Status (KPS) ≥ 50 Age ≥ 18 years Patients with metastatic melanoma and multiple skin metastases with a documented clinical progression despite the systemic treatments (chemotherapy, and/or Programmed cell death 1 (PD1), cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors or tyrosine kinase inhibitors (TKIs), such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) or mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors) The size of the treated lesions should be ≤ 5.5 cm in diameter and ≤ 2.8 cm thick (caliper-based measurement) The treated lesions should be at least 5 cm apart and must not be located on the face. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine or serum) during screening WOCBP must use a contraceptive method Exclusion Criteria: Previous radiotherapy in the treated area Concomitant auto-immune disease with skin lesions Concomitant use of radio-sensitizer drug Women who are pregnant Current, recent (within 10 days prior start of study treatment), or planned participation in an experimental drug study. During the 4 weeks DLT period, the patient will not be able to participate to any other clinical study. Any serious underlying medical condition that could interfere with study treatment and potential adverse events Any mental or other impairment that may compromise compliance with the requirements of the study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lana Kandalaft, Pharm D, PhD

Phone

+41 21 314 78 23

lana.kandalaft@chuv.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jean Bourhis, MD, PhD

Organizational Affiliation

Centre Hospitalier Universitaire Vaudois

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Universitaire Vaudois (CHUV)

City

Lausanne

State/Province

Vaud

ZIP/Postal Code

1011

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean Bourhis, MD, PhD

Phone

0041213144666

jean.bourhis@chuv.ch

12. IPD Sharing Statement

Citations:

PubMed Identifier

35736814

Citation

Maity A, Koumenis C. Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity. Clin Cancer Res. 2022 Sep 1;28(17):3636-3638. doi: 10.1158/1078-0432.CCR-22-1255.

Results Reference

derived

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