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Neoadjuvant/adjuvant IDE196 (darovasertib) in patients with primary uveal melanoma
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| darovasertib | Experimental | IDE196 (darovasertib) oral open label |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darovasertib | Drug | Oral, potent, selective inhibitor of Protein Kinase C |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events (AEs) and significant laboratory abnormalities | 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. | from first dose to 28 days after last dose of therapy, approximately 18 months |
| Cohort 1 (enucleation): Number of patients converted from requiring enucleation to radiation | Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months |
| Cohort 2 (plaque brachytherapy): Estimated change in modeled radiation dose | Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months |
| Cohort 3 (patients with small UM tumors): Number of patients with clinical benefit per protocol-defined UM response criteria | 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 | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate tumor response to neoadjuvant IDE196 | 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) | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of metastatic disease | Evaluate occurrence of metastatic uveal melanoma | from date of primary local therapy to end of follow-up, approximately 36 months |
| Overall survival | Evaluate patient survival status |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jasgit Sachdev, MD | IDEAYA Biosciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HonorHealth Research Institute | Scottsdale | Arizona | 85258 | United States | ||
| Moores Cancer Center |
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| Assessment of visual acuity loss | Best corrected visual acuity loss over time | from time of primary local therapy to one year after surgery, approximately 12 months |
| Rate of local disease recurrence | Evaluate uveal melanoma progression or recurrence | from date of primary local therapy to end of follow-up, approximately 36 months |
| Cohort 3 (patients with small UM tumors): Effect of neoadjuvant IDE196 therapy on the natural history of small UM tumors | Time from first dose of neoadjuvant to primary local therapy | from first dose of neoadjuvant to primary local therapy, approximately 12 months |
| Cohort 3 (patients with small UM tumors): Efficacy of neoadjuvant IDE196 therapy on small UM tumors | Tumor response (complete response and partial response) as measured by protocol-defined UM response criteria | from first dose of neoadjuvant to end of neoadjuvant therapy, approximately 12 months |
| from date of first dose to end of follow-up, approximately 54 months |
| La Jolla |
| California |
| 92093 |
| United States |
| Stanford Cancer Institute | Palo Alto | California | 94305 | United States |
| University of Miami | Miami | Florida | 33146 | United States |
| The Cancer and Hematology Centers | Grand Rapids | Michigan | 49546 | United States |
| Mayo Clinic Rochester | Rochester | Minnesota | 55905 | United States |
| Northwell | Manhasset | New York | 11030 | United States |
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| St. Vincent's Health Sydney | Sydney | New South Wales | 2010 | Australia |
| Alfred Health | Melbourne | Victoria | 3004 | Australia |
| Princess Margaret Cancer Centre | Toronto | Ontario | M5G2M9 | Canada |
| Institute Curie | Paris | 75005 | France |
| Charité - Universitätsmedizin Berlin | Berlin | 12203 | Germany |
| Fondazione IRCCS Istituto Nazionale Tumori | Milan | 20133 | Italy |
| Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Rome | 00168 | Italy |
| Leiden University Medical Center | Leiden | 2333 ZA | Netherlands |
| ID | Term |
|---|---|
| D000098943 | Uveal Melanoma |
| D058225 | Plaque, Amyloid |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D014604 | Uveal Neoplasms |
| D005134 | Eye Neoplasms |
| D009371 | Neoplasms by Site |
| D005128 | Eye Diseases |
| D014603 | Uveal Diseases |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
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