Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Micronutrients

All Drugs and Chemicals

Cobalt

Protontherapy : 4 sessions of 13 Gy, total dosis 52 Gy

Protontherapy : 8 sessions of 6.5 Gy, total dosis 52 Gy

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).

Protontherapy

Juliette THARIAT, md

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).

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 with 2 differents dosages of proton therapy

Study Assessing Two Models of Hypofractionated Protontherapy on Large Choroidal Melanomas

Phase II Trial, Randomized, Under Single-blind Conditions, Assessing Two Models of Modified Hypofractionated Proton-therapy on Patients With Large Choroidal Melanomas

Centre Antoine Lacassagne

Digestive System Diseases

Gastrointestinal Stromal Tumors

Fibromatosis, Aggressive

Carcinoma, Adenoid Cystic

Chordoma

Dermatofibrosarcoma

Ocular Melanoma

Desmoid Tumor

Adenoid Cystic Carcinoma

Conjunctival Melanoma

Dermatofibrosarcoma Protuberans

Antineoplastic Agents

Antirheumatic Agents

Amino Acids

Cyclophosphamide

Imatinib Mesylate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

CYCLE 1 (42 days):

* Day 1 to 14 Imatinib mesylate : 400 mg/day, per os
* Day 15 to 42 Cyclophosphamide : 50 mg x 2/day, per os Imatinib mesylate : 400 mg/day, per os

NEXT CYCLE (28 days):

Cyclophosphamide : 50 mg x 2/day, per os Imatinib mesylate : 400 mg/day, per os

Imatinib mesylate, Cyclophosphamide (Dosing level 1 )

CYCLE 1 (42 days):

* Day 1 to 14 Imatinib mesylate : 600 mg/day,(300 mg in the morning and 300 mg in the evening) per os
* Day 15 to 42 Cyclophosphamide : 50 mg x 2/day, per os Imatinib mesylate : 600 mg/day,(300 mg in the morning and 300 mg in the evening) per os

NEXT CYCLE (28 days):

Cyclophosphamide : 50 mg x 2/day, per os Imatinib mesylate : 600 mg/day,(300 mg in the morning and 300 mg in the evening)per os

Imatinib mesylate, Cyclophosphamide (Dosing level 2)

CYCLE 1 (42 days):

* Day 1 to 14 Imatinib mesylate : 800 mg/day,(400 mg in the morning and 400 mg in the evening) per os
* Day 15 to 42 Cyclophosphamide : 50 mg x 2/day, per os Imatinib mesylate : 800 mg/day,(400 mg in the morning and 400 mg in the evening) per os

NEXT CYCLE (28 days):

Cyclophosphamide : 50 mg x 2/day, per os Imatinib mesylate : 800 mg/day,(400 mg in the morning and 400 mg in the evening)per os

Imatinib mesylate, Cyclophosphamide (Dosing level 3)

ONLY FOR CYCLE 1, at day 15 and day 28 :

11 sampling for dosing level 1 (pre-dose, imatinib mesylate + 30 min, +1, +2, +3, +4, +6, +10, +12 , +24 hours, cyclophosphamide + 12 hours) 10 sampling for the next dosing level (pre-dose, imatinib mesylate + 30 min, +1, +2, +3, +4, +6, +10, +12,cyclophosphamide + 12 hours)

Blood sampling

Antoine ADENIS, MD, PhD

The purpose of this study is to determine the maximum tolerated dose of imatinib mesylate, given in association with a fixed dose of cyclophosphamide (50 mg bid).

Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate

Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate in Patient With Rare Tumor (Phase I Study)

Centre Oscar Lambret

Intraocular Melanoma

Oral, potent, selective inhibitor of Protein Kinase C

Darovasertib

IDEAYA Clinical Trials

Jasgit Sachdev, MD

Adyel Annelus

Elizabeth Seja

Claire A Billman, B.S

Denise Haas, MBA

Sarah Cannon

Clinical Trials Group

The Cancer and Hematology Centers of Western Michigan

Jessica Miller, RN

Leila Nasr, BS

Carol Ann Wiggs, BSN

Emily Bolch

Marlana Orloff, MD

Liam Hulse, BS

Ask Sarah

James Harbour, MD

Juan Mo, PhD

Chris Brooks

Marcus Butler, MD

Neoadjuvant/adjuvant IDE196 (darovasertib) in patients with primary uveal melanoma

Phase 2 multi-center open-label IDE196 study in patients with primary uveal melanoma requiring either enucleation or plaque brachytherapy. Patients will be treated in neoadjuvant setting up to 6 months (or maximum benefit) followed by primary local therapy. An additional 6 months of adjuvant treatment to follow with long term follow-up (up to 3 years) to assess visual outcome, disease recurrence, and development of metastatic disease.

(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma

Treatment emergent adverse events will be summarized by all AEs, all Grade 3-4-5 AEs, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs. Lab results will be summarized by change from baseline values, frequency of newly occurring on-treatment Grade 3 or 4 events; worst on-treatment value compared to baseline.

Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy

Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy

Measurement of tumor diameter and thickness before and after neoadjuvant therapy with IDE196, specifically as measured by ocular ultrasound, evaluating largest basal diameter and apical thickness of the uveal melanoma (measured in millimeters)

Best corrected visual acuity loss over time

Evaluate uveal melanoma progression or recurrence

Evaluate occurrence of metastatic uveal melanoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Assessing Two Models of Hypofractionated Protontherapy on Large Choroidal Melanomas	NCT02602756	Melanoma	Protontherapy	18 Years -	Centre Antoine Lacassagne
Imatinib Mesylate And Cyclophosphamide In Metronomic Administration: Dose Escalation Study Of Imatinib Mesylate	NCT01046487	Cancer	Imatinib mesyla... Imatinib mesyla... Imatinib mesyla... Blood sampling	18 Years -	Centre Oscar Lambret
(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma	NCT05907954	Uveal Melanoma	Darovasertib	18 Years -	IDEAYA Biosciences
(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma	NCT05907954	Uveal Melanoma	Darovasertib	18 Years -	IDEAYA Biosciences

Spots Global Cancer Trial Database for choroid melanoma