(Treatments to shrink tumors before surgery, radiation or other forms of nondrug therapy) to use the investigational drug (Darovasertib) in patients with a type of cancer in the middle of the eye wall.
- Conditions
- veal MelanomaMedDRA version: 21.1Level: PTClassification code: 10081431Term: Uveal melanoma Class: 100000004864Therapeutic area: Diseases [C] - Eye Diseases [C11]
- Registration Number
- CTIS2023-506683-14-00
- Lead Sponsor
- Ideaya Biosciences Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 82
Must be at least 18 years of age. Is able to provide written, informed consent before initiation of any study related-procedures, and is able, in the opinion of the Investigator, to comply with all the requirements of the study. Has an initial primary diagnosis of localized uveal melanoma (no evidence of distal and/or extraocular disease) as clinically determined by the treating Investigator, with a plan to undergo either enucleation or plaque brachytherapy. [Note: Patients with local relapse after prior primary therapies are excluded] Cohort 1: o Clinically diagnosed uveal (not iris) melanoma in which enucleation is recommended and meets the following criteria: ? Up to 22 mm in largest basal diameter (LBD) ? Up to 15 mm in thickness o NOTE: the cancer cannot have attributes that necessitate enucleation regardless of response to therapy (e.g., extraocular disease, hemorrhage, blind painful eye, evidence of optic nerve invasion, etc.) • Cohort 2: o Clinically diagnosed uveal (not iris) melanoma in which plaque brachytherapy is recommended, meets the following criteria, and places the patient at significant risk of loss of useful vision in the affected eye: ? At least 6 mm in LBD ? At least 3 mm in thickness ? NOTE: sub-foveal or >180-degree optic nerve involved tumors are excluded. Able to safely swallow orally administered medication. If prognostication and mutational status have not been evaluated as standard of care, participant must be willing to provide a buccal swab plus a fine needle aspirate (FNA) or enucleation biopsy either prior to neoadjuvant treatment or at time of primary local therapy (plaque placement or enucleation). Patient must be able to hold medications (aspirin, anticoagulation) per standard pre-operative protocols. Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 4, [Section 14.4]) (Karnofsky =70%). Lacks evidence of progressive secondary underlying ocular disease in either eye that will confound longitudinal visual acuity assessments (e.g., macular degeneration, diabetic retinopathy, neovascular glaucoma, etc). Has adequate organ function: • Absolute neutrophil count =1500/mm3 without the use of hematopoietic growth factors • Platelet count =100,000/mm3 (must be at least 2 weeks post-platelet transfusion and not receiving platelet-stimulating agents) • Hemoglobin =9.0 g/dL (must be at least 2 weeks post-red blood cell transfusion and not receiving erythropoietic-stimulating agents) • Total bilirubin =1.5 x the upper limit of normal (ULN). For patients with documented Gilbert's disease, total bilirubin =3.0 mg/dL is allowed • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 x ULN • Serum albumin =3.0 g/dL • Creatinine Clearance =60 mL/min/1.73 m2 by Cockroft-Gault equation (Appendix 1, [Section 14.1]) or serum creatinine =1.5 x ULN • Prothrombin time/International Normalized Ratio (INR) or partial thromboplastin time test results at screening =1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation) Female patients of childbearing potential must be non-pregnant, nonlactating, and have a negative serum human chorionic gonadotropin pregnancy test result within 28 days prior to the first IDE196 administration. • Females of childbearing potential who are sexually active with a nonsterilized male partner agree to use effective methods of contraception from screening (see Appendix 5 [Section 14.4]), throughout the study period and agre
Has received previous treatment with a protein kinase C (PKC) inhibitor. Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to the study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type. Has uncontrolled human immunodeficiency virus (HIV). Has active infection requiring therapy, positive tests for Hepatitis B surface antigen (HBsAg) with detected Hepatitis B virus (HBV) DNA or positive Hepatitis C antibody with detected Hepatitis C virus (HCV) ribonucleic acid (RNA). Has a malabsorption disorder that would interfere with absorption of IDE196. Requires any medication that cannot be discontinued prior to study entry and that are considered to be any of the following: • known to be strong inducers or inhibitors of cytochrome P450 (CYP)3A4/5 • known to be substrates of CYP3A4/5 with a narrow therapeutic index Known to be sensitive substrates to p-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter 3 (OAT3), multidrug and toxin extrusion (MATE)-1 and MATE-2K • drugs with a known and possible risk of QT prolongation, except for the specific use of oral granisetron, ondansetron or dolansetron for the management of nausea and vomiting (note: intravenous formulations are prohibited) Women of childbearing potential planning to become pregnant during the study. Has impaired cardiac function or clinically significant cardiac diseases, including any of the following: • History or presence of ventricular tachyarrhythmia • Presence of unstable atrial fibrillation (ventricular response >100 beats per minute); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria • Unstable angina or acute myocardial infarction =6 months prior to starting IDE196 treatment • Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or history of labile hypertension or poor compliance with an antihypertensive regimen) • Corrected QT interval using Fridericia’s formula (QTcF) >480 msec on baseline electrocardiogram (ECG) (mean of baseline values). If electrolytes are abnormal, they may be corrected and baseline electrocardiograms (ECGs) should be repeated (Appendix 2, [Section 14.2]) Has of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the Investigator, would make the patient inappropriate for entry into the study. No waivers of inclusion or exclusion criteria will be granted by the Investigator for any patient enrolled into the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the tolerability and safety of IDE196 given in the neoadjuvant and adjuvant setting and to evaluate the clinical utility of response to IDE196 in primary uveal melanomas.;Secondary Objective: To evaluate the anti-tumor activity of IDE196 as neoadjuvant therapy;Primary end point(s): • The incidence of adverse events (AEs) leading to dose interruption, modification, and discontinuation during neoadjuvant or adjuvant therapy • The incidence of Grade 3 or 4 AEs and clinically significant laboratory abnormalities during neoadjuvant or adjuvant therapy • Cohort 1 – number of patients converted from requiring enucleation to radiation (e.g., plaque brachytherapy • Cohort 2 – comparison in radiation to the fovea as modeled before and after IDE196 neoadjuvant therapy
- Secondary Outcome Measures
Name Time Method Secondary end point(s):• Bidirectional measurements which determine the T-stage (T-category) and include the apical thickness and largest basal diameter • Loss =15 letters by Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score, 1 year after completion of primary local therapy • Patients will undergo standard ophthalmology follow-up to assess for local disease progression or recurrence (local recurrence-free survival [RFS])