A Phase I/II Dose Escalation/Dose Expansion Study of Prexasertib in Combination With Irinotecan in Patients With Relapsed or RefractoryDesmoplastic Small Round Cell Tumor and Rhabdomyosarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- recommended phase II does of Prexasertib
研究概览
简要总结
The purpose of this study is to test whether the study drug prexasertib is a safe and effective treatment for people with DSRCT or RMS when given in combination with the standard drugs irinotecan and temozolomide. The study will test different doses of prexasertib in combination with irinotecan and temozolomide to find the highest dose of prexasertib that causes few or mild side effects in participants.
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
- 12 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consent/Assent: all patients and/or their parents or legally authorized representatives must sign written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
- •Age: patients must be ≥12 months of age at the time of study enrollment
- •Diagnosis: patients must have histologically documented locally advanced or metastatic desmoplastic small round cell tumor or rhabdomyosarcoma (confirmed at MSK)
- •Therapeutic options: patient's current disease state must be one which has failed standard therapy and for which there is no known curative therapy
- •Disease Status: patients must have measurable disease based on RECIST 1.1
- •Performance level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
- •Prior Therapy: patients may have had any number of prior therapies, but must have recovered from the acute toxic effects of all prior anti-cancer therapy (other than alopecia) as described below and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment
- •°patients who have previously received irinotecan and/or temozolomide will be allowed
- •21 days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy
- •7 days must have elapsed after the last dose of anti-cancer agents not known to be myelosuppressive
- •14 days must have elapsed after radiation therapy, and toxicity related to prior radiation therapy must be recovered to grade ≤ 1
- •21 days must have elapsed after the last dose of antibody therapy, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
- •Organ Function Requirements: Adequate bone marrow function defined as:
- •absolute neutrophil count (ANC) ≥ 1500/mm^3
- •platelet count ≥ 100,000/ mm^3
- •hemoglobin ≥ 8 g/dl
- •Adequate renal function defined as:
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min/1.73m2 OR
- •Serum creatinine based on age/gender derived from the Schwartz formula for estimating GFR53
- •Adequate liver function defined as:
- •Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for age
- •AST or ALT ≤ 5 x upper limit of normal for patients with liver metastases
- •Serum albumin ≥ 2.5 g/dl
- •Adequate cardiac function defined as:
- •echocardiogram with left ventricular ejection fraction (LVEF) >45%
- •QTc < 470 ms on screening 12 lead electrocardiogram
- •Pregnancy/Contraception
- •post-menarchal females must have a negative urine or serum pregnancy test at screening and ≤ 24 hours prior to study treatment
- •males or females of reproductive potential must be willing to use a barrier method of contraception throughout the course of the study and for 6 months after participation
排除标准
- •Patients for whom the investigator deems that irinotecan and temozolomide are not appropriate are not eligible.
- •Patients who have an uncontrolled infection are not eligible.
- •Patients who are pregnant or breast feeding are not eligible.
- •Patients who have a history of Torsades de Pointes, carry a diagnosis of congestive heart failure, or have a family history of prolonged QT syndrome are not eligible.
- •Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
- •Patients with known hypersensitivity to irinotecan or its excipients are not eligible.
研究组 & 干预措施
Prexasertib and Irinotecan
Patients will have extent of disease scans following every 2 cycles (every 6 weeks on dose levels 0-3, and every 8 weeks on dose level -1 (if required). Patients will be allowed to continue therapy as long as they do not experience dose-limiting toxicities or progression of disease.
干预措施: Prexasertib (Drug)
Prexasertib and Irinotecan
Patients will have extent of disease scans following every 2 cycles (every 6 weeks on dose levels 0-3, and every 8 weeks on dose level -1 (if required). Patients will be allowed to continue therapy as long as they do not experience dose-limiting toxicities or progression of disease.
干预措施: Irinotecan (Drug)
结局指标
主要结局
recommended phase II does of Prexasertib
时间窗: 1 year
The RP2D is defined as the highest dose level associated with not more than 1 DLT out of 6 patients. A total of 5 dose levels are planned, including 2 back up levels. The DLT's will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The dose escalation will follow a 3+3 design.
response
时间窗: 2 years
will be evaluated in this study using the criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline, version 1.1 (Primary response criteria)54. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
次要结局
未报告次要终点