Metastasis From Malignant Melanoma of Skin (Diagnosis)IMPulseNCT04986696
Irradiation of Melanoma in a Pulse
A study testing FLASH therapy in people with Metastasis From Malignant Melanoma of Skin (Diagnosis), run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastasis From Malignant Melanoma of Skin (Diagnosis)
- What is being tested?
- FLASH therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jul 2021to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud, 1011
Jean Bourhis, MD, PhD, 0041213144666, jean.bourhis@chuv.ch
About this study
Official title: 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.
- Being tested
- FLASH therapy
- Keywords
- FLASH therapy, melanoma
- Medical subject headings
- Disease, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLASH therapyDevice
Also called high dose rate radiotherapy
Dose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc) | Experimental | 7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy) Receives: Device: FLASH therapy |
| Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc) | Experimental | 7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy) Receives: Device: FLASH therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: from Day 1 to Day 28
Secondary outcomes (8)
Percentage of patients with Hemorrhage related to the treated lesions, assessed visually by the investigator
Hemorrhage will be visually assessed (presence/abscence)
Measured: 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
Skin ulceration will be visually assessed (presence/abscence)
Measured: 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
Pain will be assessed using an analogic visual pain scale (score from 1 to 10)
Measured: At each visit, from screening to 12 months post-treatment
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.
Measured: 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"
Measured: ≥ 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
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.
Measured: 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
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
Measured: at 4 weeks, 6 months and 12 months post-treatment
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)
Measured: within 12 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start1 Jul 2021
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastasis From Malignant Melanoma of Skin (Diagnosis)Studies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire VaudoisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation study
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jean Bourhis, Centre Hospitalier Universitaire Vaudois
- Investigators
- Jean Bourhis, MD, PhD, Principal investigator, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04986696
- Sponsor's protocol ID
- CHUV-DO-0023-IMPulse-2020
- Acronym
- IMPulse
- Status last verified
- Sep 2023
- First submitted
- 2 Jul 2021
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35736814
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, First-in-human, Dose Finding Study of High Dose Rate Radiotherapy in Patients With Skin Metastases From Melanoma
- ClinicalTrials.gov ID
- NCT04986696
- Acronym / sponsor ID
- IMPulse / CHUV-DO-0023-IMPulse-2020
- Keywords
- FLASH therapy, melanoma
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 3 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dose escalation study
| Arm | Type | Receives |
|---|---|---|
| Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc) | Experimental | Device: FLASH therapy7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy) |
| Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc) | Experimental | Device: FLASH therapy7 dose levels (22 Gy; 24 Gy; 26 Gy; 28 Gy, 30 Gy, 32 Gy and 34 Gy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLASH therapyAlso: high dose rate radiotherapyDose escalation of high dose rate radiotherapy (FLASH therapy) as single dose treatment for skin melanoma metastases that progress locally despite systemic treatments. | Device | Dose escalation of FLASH therapy in skin metastases of large volume (> 30 and ≤ 100 cc), Dose escalation of FLASH therapy in skin metastases of small volume (≤ 30 cc) |
Primary outcome
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).
8 secondary outcomes
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
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
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
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
Frequency of Late side effects observed "in radiation field"
Time frame: ≥ 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
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
Frequency of late adverse events (within 12 months post-treatment) for each dose
Time frame: within 12 months post-treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Derived from this study: PubMed 35736814Maity 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Bourhis, MD, PhD principal investigator
Centre Hospitalier Universitaire Vaudois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FLASH therapy in people with Metastasis From Malignant Melanoma of Skin (Diagnosis), run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lana Kandalaft, Pharm D, PhD (+41 21 314 78 23, lana.kandalaft@chuv.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04986696, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.