Uveal Melanoma
Conditions
Keywords
Uveal Melanoma, plaque brachytherapy, enucleation, proton beam, Adjuvant, Darovasertib, IDE 196, Ocular Melanoma, Choroidal Melanoma, Ocular Oncology, Protein Kinase C, GNAQ, GNA11, Crizotinib
Brief summary
This is a randomized, multi-center, open-label study of adjuvant darovasertib in participants with non-metastatic uveal melanoma (OptimUM-11)
Detailed description
This study will enroll participants who are at high-risk for metastatic disease and who have completed primary local therapy (i.e., plaque brachytherapy, proton beam radiation, or enucleation) for their UM without evidence of active local or metastatic disease after this treatment. The Treatment Arm will have participants who have completed PLT and will receive darovasertib + crizotinib. The Observation Arm participants will not receive darovasertib + crizotinib but will be observed and followed for disease recurrence and survival (Control Arm) Participants in both arms will be followed for up to five years to assess longer term outcomes such as tumor recurrence and survival.
Interventions
DRUGDarovasertib
Oral, selectively targets key proteins
Oral small molecule
Sponsors
IDEAYA Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary Uveal Melanoma, classified as high-risk of relapse (AJCC Stage II or Stage 3) * Completed primary local therapy (enucleation, proton beam therapy, plaque brachytherapy) * ECOG performance status of 0 or 1 * Adequate organ function * Age 18 or older * Written informed consent and ability to comply * Primary local therapy completed within 120 days before C1D1/randomization. * Contraception requirements
Exclusion criteria
* Previous systemic treatment for Uveal Melanoma * Clinical or radiological evidence of metastatic UM * Concurrent malignant disease with the following exceptions: malignancies that were treated curatively and have not recurred within 2 years prior to randomization, completely resected basal cell and squamous cell skin cancers, any malignancy considered to be indolent and never required systemic therapy, and any type of carcinoma in situ receiving curative therapy (resection) * Known AIDS related illness * History of interstitial lung disease, active pneumonitis, or history of noninfectious pneumonitis requiring steroids * History of syncope may be exclusionary, but will be reviewed on a case-by-case basis * Active Hepatitis B or C infection * Any gastrointestinal condition (eg, inflammatory bowel disease, major gastric or intestinal surgery) that could affect absorption or ability to swallow * Females who are pregnant or breastfeeding * Impaired cardiac function * History of stroke within the last 6 months of randomization * Ongoing use of medication use for infections, other antineoplastic therapies, or other prohibited medications, including medications that interact with the metabolism of darovasertib+crizotinib * allergy to mammalian meat products or gelatin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median relapse-free survival | Approximately 5 years | Time to local recurrence or metastatic disease per Blinded Independent Central Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median metastasis-free survival | Approximately 5 years | Median MFS, defined as the time from randomization to the date of metastatic disease (outside of the eye or orbit) by BICR per RECIST v 1.1 |
| Overall survival | Approximately 5 years | Overall survival with darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease who are at high-risk for recurrence |
| Median UM specific survival | Approximately 5 years | Median UM specific survival defined as the time from randomization to the date of death due to UM |
| Safety, and severity of occurrence of adverse events (AEs) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) V6.0 or later | Approximately 3 years | To assess safety and tolerability of darovasertib + crizotinib in participants who have completed PLT for primary UM |
| Change from baseline over time and across Treatment Arms as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) | Approximately 5 years | Compare quality of life outcomes of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM |
| Recurrence-free suvival | Approximately 5 years | Compare RFS of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease and who are at high-risk for recurrence |
| Metastasis-Free Survival | Approximately 5 years | Compare MFS of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease and who are at high-risk for recurrence |
| Median Local Recurrence-Free Survival | Approximately 5 years | Compare local RFS (LRFS) of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM with no evidence of metastatic disease and who are at high-risk for recurrence |
| Change from baseline over time and across Treatment Arms as measured by European Quality of Life Questionnaire EQ-5D-5L. | [Time Frame: Approximately 5 years] | Compare quality of life outcomes of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM |
| Change from baseline over time and across Treatment Arms as measured by EORTC Oncology Quality of Life Questionnaire Ophthalmic-30 (EORTC QLQ-OPT30) | [Time Frame: Approximately 5 years] | Compare quality of life outcomes of darovasertib + crizotinib versus observation in participants who have completed PLT for primary UM |
Countries
Canada, United States
Contacts
CONTACTIDEAYA Clinical Trials
CONTACTHolger Thurm
Outcome results
None listed