A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 359
- 试验地点
- 54
- 主要终点
- Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
研究概览
简要总结
This study will compare the efficacy and safety of unesbulin plus dacarbazine versus placebo plus dacarbazine in participants with unresectable or metastatic, relapsed or refractory LMS who have received at least 1 prior line of systemic therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Histological or cytological confirmation of LMS arising at any anatomic site except bone sarcoma, unresectable or metastatic, relapsed or refractory disease measurable per RECIST 1.1 criteria
- •Disease progression on previous treatment before screening or intolerability to other oncology treatments
- •Participants with liver metastases may be enrolled
- •Participants with well-controlled asthma or chronic obstructive pulmonary disease may be enrolled.
- •Toxicity from prior therapies recovered to Grade ≤1 or participant's baseline, except for alopecia. In addition, endocrinopathies associated with prior immunotherapy-based treatments that are well controlled on replacement medication are not exclusionary.
- •At least 1 prior systemic cytotoxic or targeted therapy regimen for LMS, which may include but is not limited to single-agent doxorubicin or other anthracycline, doxorubicin plus ifosfamide, trabectedin, pazopanib, or gemcitabine with or without docetaxel.
- •At least 4 weeks since prior surgery and recovered in the opinion of investigator
排除标准
- •Received temozolomide or dacarbazine at any time
- •Any other systemic anticancer therapy including investigational agents ≤3 weeks before initiation of study treatment. Additionally, participants may not have received radiation ≤3 weeks before initiation of study treatment.
- •Known intolerance to dacarbazine or one or more of the excipients in unesbulin.
- •Co-existing active infection or any co-existing medical condition likely to interfere with study procedures
- •Gastrointestinal disease or other conditions that could affect absorption. Active peptic ulcer disease, active gastritis, or previous history of gastric perforation within the last 2 years
- •Major surgery, open biopsy, or significant traumatic injury that has not recovered, in the opinion of the investigator, within 28 days of baseline
- •Immunization with a live vaccine within 30 days before starting study drug due to the risk of serious and life-threatening infections.
- •Prior malignancies, other than LMS, that required treatment or have shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ, prostate cancer in situ or any other low risk malignancy that is approved by the medical monitor) during the 5 years before initiation.
- •Prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results.
- •Note: Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Unesbulin and Dacarbazine
Participants will receive unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/meter squared (m^2) intravenously (IV) once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
干预措施: Unesbulin (Drug)
Unesbulin and Dacarbazine
Participants will receive unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/meter squared (m^2) intravenously (IV) once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
干预措施: Dacarbazine (Drug)
Placebo and Dacarbazine
Participants will receive placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
干预措施: Dacarbazine (Drug)
Placebo and Dacarbazine
Participants will receive placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment will continue for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
干预措施: Placebo (Other)
结局指标
主要结局
Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
时间窗: Up to approximately 2 years
PFS was defined as the time from randomization to the documented disease progression or death due to any cause, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression.
次要结局
- Overall Survival(Up to approximately 2 years)
- Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1(Up to approximately 2 years)
- Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1(Up to approximately 2 years)
- Duration of Response Per Independent Central Review Using RECIST V1.1(Up to approximately 2 years)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug up to approximately 2 years)