MelanomaHYGROMELNCT02602756
Study Assessing Two Models of Hypofractionated Protontherapy on Large Choroidal Melanomas
A study testing Protontherapy in people with Melanoma, run by Centre Antoine Lacassagne at 1 site in France.
Trial summary
Ocular melanomas have been treated for a long time by enucleation, with an unfavorable major impact on the patient's quality of life, social life, self-image, how they feel about others and about living with this disability. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Protontherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 2 Nov 2015to 30 Nov 2022
- 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
- Patient diagnosed with choroidal melanoma by an ophthalmologist and proton-therapy treatment proposed by the multi-disciplinary board meeting
- Patient over 18 years old, male or female
- Performance status ≤ 2
- Size and/or thickness greater than those proposed on proton-therapy appendix indications (tumor volume/ocular globe > 40% and/or thickness ≥ 12 mm and/or diameter ≥ 18 mm or thickness ≥ 10 mm and diameter ≥ 15 mm). Possible ophthalmological follow-up examinations at 6 months, one year, 18 months and two years.
- No contraindication for adjuvant chemotherapy
- Authorized technique to preserve the optic nerve
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- Patient having undergone the required medical procedures:
- Ophthalmological examination
- Clip positioning
- Proton-therapy treatment (localization CT, first simulation, second simulation, final simulation)
- Patient reads information note and signs consent form
Who cannot join
- Exclusive iris damage
- Exclusive conjunctival damage
- First melanoma surgery
- Enucleation planned post-proton-therapy
- Exentration indication
- Life expectancy < 2 years
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- Scleral exteriorisation > 2 mm
- Absolute radiotherapy contraindication (ataxia-telangiectasia)
- Cancer history, except for complete remission cancers of over 5 years, basocellular skin carcinomas completely resected, in-situ carcinomas or treated in situ cervical epithelioma
- Presence of metastases other than hepatic (endoresection authorized)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial, Randomized, Under Single-blind Conditions, Assessing Two Models of Modified Hypofractionated Proton-therapy on Patients With Large Choroidal Melanomas
Ocular melanomas have been treated for a long time by enucleation, with an unfavorable major impact on the patient's quality of life, social life, self-image, how they feel about others and about living with this disability. As a matter of fact, classical radiation therapy by photons is not accurate enough to deliver a sufficiently high dose to eradicate a melanoma without causing irreversible ocular brain complications since these tumors are " relatively radio resistant ". The possibility of delivering high doses due to the precision of protons ("Bragg peak") has allowed to overcome this limitation. The conservative uveal melanoma treatment has become a standard after the Collaborative Ocular Melanoma Study (COMS) indicating an equivalent rate of metastases and a non-impaired survival rate with a conservative treatment when compared to immediate enucleation. The quality of life benefits due to a conservative treatment has been demonstrated. Protontherapy dose has been defined in an empirical manner, it is probably excessive even if it applies to radio-resistant tumors. In France, radiotherapy by protons for choroidal melanomas delivers a dose of 60 Gy cobalt equivalent (that is 52 measured Gy, or " Physical dose") in 4 fractions and 4 days.
Referential treatment of ocular melanomas (other than conjunctiva) indicates proton-therapy for T1, T2, T3 < 40% of ocular volume, and T4 only if extra scleral extension ≤ 2mm. However, there is an enucleation indication for T3 > 40% of ocular volume and T4.
Our purpose is to override this relative contraindication, choroidal melanoma volume ≥ 40% of ocular volume. As a matter of fact, the investigators observe an increasing demand from ophthalmologists and patients for not performing primary enucleation. Also, during the last five years treatment of complications have improved and a less " hard " hypo fractionation (6.5 Gy per fraction) has equivalent local control results as for " hard " fractionation (13 Gy per fraction).
Read the detailed description
A more fractioned proton-therapy treatment, with doses per fraction of 6.5 Gy rather than 13 Gy, can limit the rate and the severity of complications degrading the quality of life by complications (pain, diminished visual acuity) and treatments (intra-ocular injections...).
In this study, patients will receive a total dose of 52 Gy in four 13 Gy sessions for the standard arm and in eight 6.5 Gy sessions for the experimental arm.
The investigators expect an identical local control rate within 2 year's time with a decrease in rate and severity of severe complications due to adapted fractionation (eight sessions with lower doses instead of four fractions with very high doses as it is usually recommended in the guidelines for small to medium melanomas).
- Conditions
- Melanoma
- Being tested
- Protontherapy
- Keywords
- Choroid Melanoma
- Medical subject headings
- Melanoma, Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProtontherapyRadiation
Proton-therapy consists in four consecutive sessions. The experimental arm consists in eight sessions. Irradiation is administered over two weeks, delivering a total dose of 60 Cobalt Gris Equivalent (CGE is the physical Gray dose multiplied by a biological factor of relative efficiency of 1.1 for protons compared to photons).
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Protontherapy : 4 sessions of 13 Gy, total dosis 52 Gy Receives: Radiation: Protontherapy |
| B | Experimental | Protontherapy : 8 sessions of 6.5 Gy, total dosis 52 Gy Receives: Radiation: Protontherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
local control rate without severe complications 2 years after.
Measured: up to 60 months
Secondary outcomes (5)
Enucleation rate
Measured: up to 60 months
Tumoral transretinien endoresection by unplanned vitrectomy in inclusion (emergency procedure)
Measured: up to 60 months
Number of months without metastases evaluation
Measured: up to 60 months
Number of months of Specific global survival evaluation
Measured: up to 60 months
Complications and toxicity evaluation (number of subjects with adverse events related to treatment)
Measured: up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2015 (estimated)
- Study start2 Nov 2015
- Primary completion1 Sep 2018
- Study completion30 Nov 2022
Why it stopped: insufficient quality of data collection
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 MelanomaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study with 2 differents dosages of proton therapy
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Antoine Lacassagne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juliette THARIAT, md, Principal investigator, Centre Antoine Lacassagne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02602756
- Sponsor's protocol ID
- 2015/02
- Acronym
- HYGROMEL
- Status last verified
- Jun 2026
- First submitted
- 9 Nov 2015
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Thariat J, Mathis T, Pace-Loscos T, Peyrichon ML, Maschi C, Rosier L, Nguyen M, Bonnin N, Aloi D, Gastaud L, Gaucher D, Caujolle JP, Chateau Y, Herault J. Single-Masked Randomized Phase 2 Study Assessing 2 Forms of Hypofractionated Proton Therapy in Patients With Large Choroidal Melanomas. Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2):357-369. doi: 10.1016/j.ijrobp.2023.04.028. Epub 2023 May 29.
PubMed 37257661
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial, Randomized, Under Single-blind Conditions, Assessing Two Models of Modified Hypofractionated Proton-therapy on Patients With Large Choroidal Melanomas
- ClinicalTrials.gov ID
- NCT02602756
- Acronym / sponsor ID
- HYGROMEL / 2015/02
- Conditions
- Melanoma
- Keywords
- Choroid Melanoma
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient quality of data collection
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Centre Antoine LacassagneUniversity, hospital or other
- Study start
- 2 Nov 2015 (actual)
- Primary completion
- 1 Sep 2018 (actual)
- Study completion
- 30 Nov 2022 (actual)
- First posted
- 11 Nov 2015 (estimated)
- 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.
Ocular melanomas have been treated for a long time by enucleation, with an unfavorable major impact on the patient's quality of life, social life, self-image, how they feel about others and about living with this disability. As a matter of fact, classical radiation therapy by photons is not accurate enough to deliver a sufficiently high dose to eradicate a melanoma without causing irreversible ocular brain complications since these tumors are " relatively radio resistant ". The possibility of delivering high doses due to the precision of protons ("Bragg peak") has allowed to overcome this limitation. The conservative uveal melanoma treatment has become a standard after the Collaborative Ocular Melanoma Study (COMS) indicating an equivalent rate of metastases and a non-impaired survival rate with a conservative treatment when compared to immediate enucleation. The quality of life benefits due to a conservative treatment has been demonstrated. Protontherapy dose has been defined in an empirical manner, it is probably excessive even if it applies to radio-resistant tumors. In France, radiotherapy by protons for choroidal melanomas delivers a dose of 60 Gy cobalt equivalent (that is 52 measured Gy, or " Physical dose") in 4 fractions and 4 days.
Referential treatment of ocular melanomas (other than conjunctiva) indicates proton-therapy for T1, T2, T3 < 40% of ocular volume, and T4 only if extra scleral extension ≤ 2mm. However, there is an enucleation indication for T3 > 40% of ocular volume and T4.
Our purpose is to override this relative contraindication, choroidal melanoma volume ≥ 40% of ocular volume. As a matter of fact, the investigators observe an increasing demand from ophthalmologists and patients for not performing primary enucleation. Also, during the last five years treatment of complications have improved and a less " hard " hypo fractionation (6.5 Gy per fraction) has equivalent local control results as for " hard " fractionation (13 Gy per fraction).
Detailed description
A more fractioned proton-therapy treatment, with doses per fraction of 6.5 Gy rather than 13 Gy, can limit the rate and the severity of complications degrading the quality of life by complications (pain, diminished visual acuity) and treatments (intra-ocular injections...).
In this study, patients will receive a total dose of 52 Gy in four 13 Gy sessions for the standard arm and in eight 6.5 Gy sessions for the experimental arm.
The investigators expect an identical local control rate within 2 year's time with a decrease in rate and severity of severe complications due to adapted fractionation (eight sessions with lower doses instead of four fractions with very high doses as it is usually recommended in the guidelines for small to medium melanomas).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Study with 2 differents dosages of proton therapy
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Radiation: ProtontherapyProtontherapy : 4 sessions of 13 Gy, total dosis 52 Gy |
| B | Experimental | Radiation: ProtontherapyProtontherapy : 8 sessions of 6.5 Gy, total dosis 52 Gy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient diagnosed with choroidal melanoma by an ophthalmologist and proton-therapy treatment proposed by the multi-disciplinary board meeting
- Patient over 18 years old, male or female
- Performance status ≤ 2
- Size and/or thickness greater than those proposed on proton-therapy appendix indications (tumor volume/ocular globe > 40% and/or thickness ≥ 12 mm and/or diameter ≥ 18 mm or thickness ≥ 10 mm and diameter ≥ 15 mm). Possible ophthalmological follow-up examinations at 6 months, one year, 18 months and two years.
- No contraindication for adjuvant chemotherapy
Key exclusion criteria (10 listed)
- Exclusive iris damage
- Exclusive conjunctival damage
- First melanoma surgery
- Enucleation planned post-proton-therapy
- Exentration indication
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 |
|---|---|---|
| ProtontherapyProton-therapy consists in four consecutive sessions. The experimental arm consists in eight sessions. Irradiation is administered over two weeks, delivering a total dose of 60 Cobalt Gris Equivalent (CGE is the physical Gray dose multiplied by a biological factor of relative efficiency of 1.1 for protons compared to photons). | Radiation | A, B |
Primary outcome
local control rate without severe complications 2 years after.
Time frame: up to 60 months
5 secondary outcomes
Enucleation rate
Time frame: up to 60 months
Tumoral transretinien endoresection by unplanned vitrectomy in inclusion (emergency procedure)
Time frame: up to 60 months
Number of months without metastases evaluation
Time frame: up to 60 months
Number of months of Specific global survival evaluation
Time frame: up to 60 months
Complications and toxicity evaluation (number of subjects with adverse events related to treatment)
Time frame: up to 60 months
Results and safety
The study was stopped early (reason given: insufficient quality of data collection). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Results publication: PubMed 37257661Thariat J, Mathis T, Pace-Loscos T, Peyrichon ML, Maschi C, Rosier L, Nguyen M, Bonnin N, Aloi D, Gastaud L, Gaucher D, Caujolle JP, Chateau Y, Herault J. Single-Masked Randomized Phase 2 Study Assessing 2 Forms of Hypofractionated Proton Therapy in Patients With Large Choroidal Melanomas. Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2):357-369. doi: 10.1016/j.ijrobp.2023.04.028. Epub 2023 May 29.
- Related InfoLink provided by the sponsor.
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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.
Juliette THARIAT, md principal investigator
Centre Antoine Lacassagne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protontherapy in people with Melanoma, run by Centre Antoine Lacassagne at 1 site in France.
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 11 inclusion and 10 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: stopped early, as of the sponsor's last update on 12 Jun 2026. 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 France. 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?
The study was stopped early (reason given: insufficient quality of data collection). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
local control rate without severe complications 2 years after. (time frame: up to 60 months). 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 NCT02602756, 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 12 Jun 2026.