Irradiation of Melanoma in a Pulse (IMPulse)

September 19, 2023 updated by: Jean Bourhis, Centre Hospitalier Universitaire Vaudois

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Switzerland
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois (Chuv)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed study Informed Consent Form
  2. Karnofsky Performance Status (KPS) ≥ 50
  3. Age ≥ 18 years
  4. 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)
  5. The size of the treated lesions should be ≤ 5.5 cm in diameter and ≤ 2.8 cm thick (caliper-based measurement)
  6. The treated lesions should be at least 5 cm apart and must not be located on the face.
  7. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine or serum) during screening
  8. WOCBP must use a contraceptive method

Exclusion Criteria:

  1. Previous radiotherapy in the treated area
  2. Concomitant auto-immune disease with skin lesions
  3. Concomitant use of radio-sensitizer drug
  4. Women who are pregnant
  5. 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.
  6. Any serious underlying medical condition that could interfere with study treatment and potential adverse events
  7. Any mental or other impairment that may compromise compliance with the requirements of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc)
7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy)
Device: FLASH therapy
Dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments.
Other Names:
  • high dose rate radiotherapy
Experimental: Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc)
7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy)
Device: FLASH therapy
Dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments.
Other Names:
  • high dose rate radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of maximum tolerated dose (MTD) or recommended phase II dose (RP2D), separately for skin metastases of small and large volumes.
Time Frame: from Day 1 to Day 28
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).
from Day 1 to Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator
Time Frame: At each visit, from screening to 12 months post-treatment
Hemorrhage will be visually assessed (presence/abscence)
At each visit, from screening to 12 months post-treatment
Percentage of patients with Skin ulceration related to the treated lesions, assessed visually by the investigator
Time Frame: At each visit, from screening to 12 months post-treatment
Skin ulceration will be visually assessed (presence/abscence)
At each visit, from screening to 12 months post-treatment
Percentage of patients with Pain related to the treated lesions, assessed with analogic visual pain scale
Time Frame: At each visit, from screening to 12 months post-treatment
Pain will be assessed using an analogic visual pain scale (score from 1 to 10)
At each visit, from screening to 12 months post-treatment
Local response of metastases "in the radiation field", measured with calipers
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
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.
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
Frequency of Late side effects observed "in radiation field"
Time Frame: ≥ 6 months post-treatment
≥ 6 months post-treatment
Blinded Imaging Central Review (BICR) of photographs evaluating both tumor response and "in radiation field" normal tissue responses around the treated tumors
Time Frame: From Day 1 up to 12 months post-treatment
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.
From Day 1 up to 12 months post-treatment
Optical coherence tomography (OCT) examination of the irradiated skin compared to the normal non-irradiated skin
Time Frame: at 4 weeks, 6 months and 12 months post-treatment
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
at 4 weeks, 6 months and 12 months post-treatment
Frequency of late adverse events (within 12 months post-treatment) for each dose
Time Frame: within 12 months post-treatment
Long-term safety of RT procedure will be measured as recording of late adverse events (CTCAE v5.0)
within 12 months post-treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: within 12 months post-treatment (at 1, 3, 4, 6 weeks post-treatment; at 3, 6, 12 months post-treatment; at progression)
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
within 12 months post-treatment (at 1, 3, 4, 6 weeks post-treatment; at 3, 6, 12 months post-treatment; at progression)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire Vaudois

Investigators

  • Principal Investigator: Jean Bourhis, MD, PhD, Centre Hospitalier Universitaire Vaudois

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

July 2, 2021

First Submitted That Met QC Criteria

July 29, 2021

First Posted (Actual)

August 3, 2021

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 19, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUV-DO-0023-IMPulse-2020

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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