2023-506683-14-00招募中2 期
(Neo)adjuvant IDE196 (Darovasertib) in Patients with Localized Ocular Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 21
- 试验地点
- 7
- 主要终点
- The incidence of adverse events (AEs) leading to dose interruption, modification, and discontinuation during neoadjuvant therapy • The incidence of Grade 3 or 4 AEs and clinically significant laboratory abnormalities during neoadjuvant therapy
研究概览
简要总结
-To evaluate the tolerability and safety of IDE196 given in the neoadjuvant setting. -To evaluate the clinical utility of tumor shrinkage in response to neoadjuvant IDE196 in primary UM UM (Cohorts 1 and 2) -To evaluate neoadjuvant IDE196 treatment with respect to clinical benefit rate (CBR) (Cohort 3)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •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 UM (no evidence of distant 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.) Tumor must be able to be completely imaged by ocular ultrasound and color fundus photography for accurate tumor measurements and distance to vital eye structures, such as the fovea and optic disc. • Cohort 1: o Clinically diagnosed uveal (not iris) melanoma in which enucleation is recommended and meets the following criteria: > 10 mm in thickness (or in regions where non-I125 plaque is standard of care, > 6 mm for non-I125 plaques) Tumor must not exceed 16 mm in LBD to be considered eligible. 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 to an extent that despite tumor shrinkage eye preservation is not reasonably expected; 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: 4-10 mm in thickness (or in regions where non-I125 plaque is standard of care, 4-6 mm for non-I125 plaques) Tumor must not exceed 16 mm in LBD to be considered eligible. • 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: 4-10 mm in thickness (or in regions where non-I125 plaque is standard of care, 4-6 mm for non-I125 plaques) Tumor must not exceed 16 mm in LBD to be considered eligible. o NOTE: Sub-foveal or > 180-degree optic nerve involved tumors are excluded. At least 10 subjects from Cohort 2 will participate in the PK substudy. • Cohort 3: o Clinically diagnosed uveal (not iris) melanoma that is < 4 mm in thickness requiring treatment Tumor must not exceed 12 mm in LBD to be considered eligible. o NOTE: at least half the subjects must have a tumor that is ≤ 3 mm in thickness. Approximately 10 subjects in Cohort 3 will participate in the PK substudy. Lesions that are indeterminate or are nevi are excluded.
- •Able to safely swallow orally administered medication.
- •Has available prognostication results assessed by local standards, or patient must be willing to submit sample(s) (prior to neoadjuvant therapy or at the time of PLT) for local or central laboratory prognostication testing. If prognostication results are not available and sample(s) cannot be collected, a patient may be enrolled only after approval by the Medical Monitor.
- •Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 4, [Section 14.4]) (or Karnofsky ≥70%).
- •No 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 × 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 × ULN • Serum albumin ≥3.0 g/dL • Creatinine clearance ≥45 mL/min by Cockroft-Gault equation (Appendix 1, [Section 14.1]). Patients with creatine clearance between 30 and 45 mL/min can be considered for eligibility in discussion with the Medical Monitor.• Prothrombin time/International Normalized Ratio (INR) or partial thromboplastin time test results at screening ≤1.5 × ULN (this applies only to patients who do not receive therapeutic anticoagulation)
- •Female patients of childbearing potential must be non-pregnant, non-lactating, 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 non-sterilized male partner agree to use effective methods of contraception from screening (see Appendix 5 [Section 14.5]), throughout the study period and agree to continue using such precautions for 30 days after the final dose of IDE196 as a monotherapy. Systemically acting hormonal contraceptives should always be combined with a barrier method (preferably male condom). • Non-sterilized males who are sexually active with a female of childbearing potential must agree to use effective methods of contraception, including condom, from Day 1 throughout the study period and for 90 days after the final dose of IDE196 as a monotherapy treatment.
排除标准
- •Has received previous treatment with a 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 carcinomas; any malignancy considered to be indolent and that has never required systemic therapy; and completely resected carcinomas 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 IDE
- •Requires any medication that cannot be discontinued prior to study entry and that is 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 (NTI) • Known to be a sensitive substrate of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) with an NTI.
- •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). Abnormal electrolytes at Screening such as low potassium or magnesium, which may cause QT prolongation, can be corrected and then the baseline ECG repeated. (Appendix 2, [Section 14.2]).
- •Has any other condition or circumstances that may increase the risk associated with study participation or may interfere with the interpretation of study results and/or, in the opinion of the Investigator, would make the patient inappropriate for entry into the study.
结局指标
主要结局
The incidence of adverse events (AEs) leading to dose interruption, modification, and discontinuation during neoadjuvant therapy • The incidence of Grade 3 or 4 AEs and clinically significant laboratory abnormalities during neoadjuvant therapy
The incidence of adverse events (AEs) leading to dose interruption, modification, and discontinuation during neoadjuvant therapy • The incidence of Grade 3 or 4 AEs and clinically significant laboratory abnormalities during neoadjuvant therapy
Cohort 1 – Percentage of patients converted from planned enucleation to eye preserving therapy (e.g., plaque brachytherapy, proton beam radiotherapy, or other) • Cohort 2 –Percentage of patients with a reduction in radiatiAon dose to the fovea, optic disc center, or optic nerve determined by independent central dosimetry modeling
Cohort 1 – Percentage of patients converted from planned enucleation to eye preserving therapy (e.g., plaque brachytherapy, proton beam radiotherapy, or other) • Cohort 2 –Percentage of patients with a reduction in radiatiAon dose to the fovea, optic disc center, or optic nerve determined by independent central dosimetry modeling
Proportion of subjects with CBR defined as complete response (CR) + partial response (PR) + stable disease (SD) ≥ 12 weeks per the UM response criteria
Proportion of subjects with CBR defined as complete response (CR) + partial response (PR) + stable disease (SD) ≥ 12 weeks per the UM response criteria
次要结局
- Time from first dose to time of primary local therapy
- Tumor response (CR + PR)
- Decrease in tumor apical height or bidirectional measurements that include the apical height (tumor thickness) and LBD
- Loss of ≥ 15 letters by Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) letter score
- Local disease recurrence rate
研究者
Candice Montagna
Scientific
Ideaya Biosciences Inc.
研究点 (7)
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