NCT03391050终止1 期
A Phase Ib/II Study to Investigate the Safety and Clinical Activity of APR-246 in Combination With Dabrafenib in Patients With BRAF V600 Mutant Unresectable and/or mEtastatic Cutaneous MElanoma Resistant to Dabrafenib/Trametinib Combination
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 3
- 主要终点
- Phase Ib: Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to make a preliminary assessment of the efficacy of a combined APR-246 and dabrafenib therapy regimen in patients with BRAFV600 mutant unresectable and/or metastatic cutaneous melanoma resistant to the dabrafenib/trametinib combination. In addition, the study aims to assess the safety profile of the combined APR-246 and dabrafenib therapy regimen, to explore potential biomarkers, and to further describe the anti-tumour activity of the combination of APR-246 and dabrafenib. The trial will enroll up to 31 evaluable patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with confirmed BRAF V600 mutation-positive unresectable and/or metastatic malignant cutaneous melanoma, as determined locally by a validated test and treated with dabrafenib/trametinib first line combination therapy or second line after first line immunotherapy.
- •Patients that have progressed according to RECIST 1.1 after at least 4 weeks of treatment with dabrafenib/trametinib and remained on dabrafenib full dose (150mg bid) treatment for the study.
- •Measurable disease according to RECIST 1.1 criteria. For phase II only, metabolic measurable disease (according to PERCIST).
- •Availability of tissue from a metastatic lesion. A new biopsy is required unless inaccessible. An archival sample is accepted in that case after discussion with the sponsor.
- •ECOG Performance Status of 0 or
- •Patients able to swallow and retain oral medication.
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- •For female patients of childbearing potential, a pregnancy test (serum) will be performed within 7 days before inclusion. Woman of childbearing potential must be willing to use one highly effective form of contraception during anticancer treatment and for at least six months thereafter. Men must agree to use condom during the course of this study and at least six months after the last administration of the study treatment and contraception should be considered for partner of childbearing potential.
- •Adequate organ system function.
- •Signed informed consent before any study specific procedure and/or treatment happens.
排除标准
- •Presence of uveal melanoma and/or other non-cutaneous melanomas.
- •Current use of a prohibited medication or need for any of these medications during treatment with study drug and within 28 days before the first administration of APR-
- •I.e., no anti-cancer other than that given in this clinical trial, no immunotherapy, no hormonal cancer therapy, no radiation therapy (except palliative) and no experimental medications are permitted during the trial. All alternative therapies must first be approved by the sponsor. Supportive care therapies are allowed.
- •Unresolved toxicity greater than NCI-CTCAE(v4) Grade 1 from previous anti-cancer therapy except alopecia.
- •Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- •Known HIV, active hepatitis B or hepatitis C infection.
- •Primary malignancy of the central nervous system.
- •History of familial long QT, serious ventricular arrhythmia (no VT > 130 bpm and > 5 extra beats per minute), no QTc ≥ 480 msec calculated from a single ECG reading or a mean of 3 ECG readings using Fridericia's correction (QTcF = QT/RR0.33) or bradycardia (< 45 bpm).
- •Untreated or symptomatic brain metastasis, leptomeningeal disease or spinal cord compression. Patients who are on a stable dose of corticosteroids > 1 month or off corticosteroids for 2 weeks can be enrolled.
- •History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting, or thrombo-embolic event within the past 24 weeks from signature of ICF.
- •Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients.
- •Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity.
- •Pregnant or lactating woman.
研究组 & 干预措施
APR-246 + Dabrafenib
Experimental
干预措施: APR-246 (Drug)
APR-246 + Dabrafenib
Experimental
干预措施: Dabrafenib (Drug)
结局指标
主要结局
Phase Ib: Adverse Events (AEs)
时间窗: Up to 30 days after last study treatment day, or at end of study visit due to progression, whichever occurs later (treatment cycles are stopped due to progression, toxicity or patient's decision)
Clinical and laboratory adverse events (AEs) and serious adverse events (SAEs) will be reported and graded
Phase Ib: Dose Limiting Toxicities (DLTs)
时间窗: Until end of cycle 1 (cycle length is 28 days)
Phase II: Objective response rate by RECIST1.1
时间窗: Until progression (assessed up to 12 months)
次要结局
- Progression free survival (PFS)(Until progression (assessed up to 12 months))
- Plasma drug concentration at a specified time t (Ct) for APR-246(Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II))
- Clinical benefit rate(Until progression (assessed up to 12 months))
- Time to reach maximum plasma concentration following drug administration (tmax) for APR-246(Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II))
- Maximum observed plasma concentration (Cmax) of APR-246(Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II))
- Duration of response(Until progression (assessed up to 12 months))
- Area under the plasma concentration versus time curve (AUC) for APR-246(Until Cycle 1 Day 8 (Phase Ib) or Cycle 1 Day 1 (Phase II))
- Assessment of metabolic response(Until Cycle 2 Day 1 (cycle length is 28 days))
研究者
研究点 (3)
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