Uveal Melanoma
Conditions
Keywords
Uveal Melanoma, Plaque brachytherapy, Enucleation, Neoadjuvant, Adjuvant, Protein Kinase C, Ophthalmology, Ocular Oncology, Darovasertib, IDE196, Ocular melanoma, Choroid melanoma, Plaque, Brachytherapy
Brief summary
Neoadjuvant/adjuvant IDE196 (darovasertib) in patients with primary uveal melanoma
Detailed description
Phase 2 multi-center open-label IDE196 study in patients with primary uveal melanoma (UM) requiring either enucleation or plaque brachytherapy. Patients will be treated in neoadjuvant setting up to 12 months (or maximum benefit) followed by primary local therapy. An additional 6 months of adjuvant treatment may be given to some patients. All patients will have long term follow-up (up to 3 years) to assess visual outcome, disease recurrence, and development of metastatic disease.
Interventions
DRUGDarovasertib
Oral, potent, selective inhibitor of Protein Kinase C
Sponsors
IDEAYA Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary localized uveal melanoma requiring either enucleation or plaque brachytherapy * Cohort 3 (patients with small UM tumors) - clinically diagnosed uveal (not iris) melanoma that is \< 4 mm in thickness requiring treatment * Able to dose orally * ECOG Performance status of 0-1 * No other significant underlying ocular disease * Adequate organ function * Not pregnant/nursing or planning to become pregnant. Willing to use birth control
Exclusion criteria
* Previous treatment with a Protein Kinase C (PKC) inhibitor * Concurrent malignant disease * Active HIV infection or Hep B/C * Malabsorption disorder * Unable to discontinue prohibited medication * Impaired cardiac function or clinically significant cardiac disease * Any other condition which may interfere with study interpretation or results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 2 (plaque brachytherapy): Estimated change in modeled radiation dose | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months | Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy |
| Incidence of Adverse Events (AEs) and significant laboratory abnormalities | from first dose to 28 days after last dose of therapy, approximately 18 months | 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. |
| Cohort 1 (enucleation): Number of patients converted from requiring enucleation to radiation | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months | Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy |
| Cohort 3 (patients with small UM tumors): Number of patients with clinical benefit per protocol-defined UM response criteria | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months | Proportion of patients with clinical benefit rate (CBR) defined as complete response (CR) + partial response (PR) + stable disease (SD) for ≥ 12 weeks per UM response criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate tumor response to neoadjuvant IDE196 | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months | 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) |
| Assessment of visual acuity loss | from time of primary local therapy to one year after surgery, approximately 12 months | Best corrected visual acuity loss over time |
| Rate of local disease recurrence | from date of primary local therapy to end of follow-up, approximately 36 months | Evaluate uveal melanoma progression or recurrence |
| Cohort 3 (patients with small UM tumors): Effect of neoadjuvant IDE196 therapy on the natural history of small UM tumors | from first dose of neoadjuvant to primary local therapy, approximately 12 months | Time from first dose of neoadjuvant to primary local therapy |
| Cohort 3 (patients with small UM tumors): Efficacy of neoadjuvant IDE196 therapy on small UM tumors | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months | Tumor response (complete response and partial response) as measured by protocol-defined UM response criteria |
Countries
Australia, Canada, France, Germany, Italy, Netherlands, United States
Contacts
STUDY_DIRECTORJasgit Sachdev, MD
IDEAYA Biosciences
Outcome results
None listed