A Pilot Study of BTX-A51 in Patients With Metastatic and/or Recurrent Liposarcomas Characterized by MDM2 Amplifications, Myxoid Liposarcoma, and CIC-Rearranged Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 3
- 主要终点
- Number of participants with adverse events, with laboratory abnormalities, with dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event
研究概览
简要总结
This study is testing two different doses of BTX-A51 to determine if it is safe and tolerable in participants with liposarcoma with MDM2 amplification, myxoid liposarcoma, and CIC-rearranged sarcoma.
The name of the study drug used in this research study is:
-BTX-A51 (a type of kinase inhibitor)
详细描述
This is a two-cohort, pilot study assessing the safety and preliminary exploration of BTX-A51 at two dose levels in participants with metastatic and/or recurrent liposarcomas characterized by Murine Double Minute Clone 2 (MDM2) amplifications (i.e. de-differentiated and /or well-differentiated liposarcomas), myxoid liposarcoma, and CIC-rearranged sarcomas. BTX-A51 works in a different way from currently approved therapies used to treat liposarcoma by blocking proteins called CK1α and CDK9.
The U.S. Food and Drug Administration (FDA) has not approved BTX-A51 as a treatment for liposarcoma characterized by MDM2 amplifications, myxoid liposarcoma, or CIC-rearranged sarcomas.
The research study procedures include screening for eligibility, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission Tomography (PET) scans, blood tests, and tumor biopsies.
Participants will receive study treatment for as long as there are no serious side effects, and disease does not get worse. Participants will be followed for 1 year after the last dose of BTX-A51.
It is expected that about 24 people will take part in this research study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Study participants must have histologically-confirmed metastatic and/or recurrent liposarcoma (limited to the subtypes of well-differentiated and/or dedifferentiated liposarcoma, which are associated with MDM2 amplifications), or myxoid liposarcoma, or CIC-rearranged sarcoma.
- •ECOG performance status ≤2
- •Adequate organ and marrow function as defined by the following metrics resulted within 7 days of study enrollment:
- •WBC >3000/mm3
- •Platelets >75,000μl
- •ANC >1500μl
- •Hgb >9g/dl
- •Creatinine <1.5 x ULN or measured CrCl of >60ml/m2/1.73 m2
- •Total bilirubin <2 x ULN
- •AST/ALT <3 x ULN
- •Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as
- •≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
- •Patients must have recovered from toxicity related to prior therapy to grade <=1 (defined by CTCAE v5.0) (except alopecia and neuropathy, or immunotherapy related hypothyroidism)
- •As the effect of this study drug on the developing human fetus is not known, women of child-bearing potential and men must agree to use at least 2 methods of contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion.
- •Female patient of childbearing potential has a negative serum pregnancy test within 7 days of study enrollment.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Age ≥18 years
- •Patients must have completed all prior anti-cancer treatment for liposarcoma, including radiation, ≥ 14 days prior to registration.
排除标准
- •Patient with current evidence of active and uncontrolled infection, NYHA Class III-IV CHF, documented Child's class B-C cirrhosis, or uncontrolled medical disease which in the opinion of the investigator or the sponsor could compromise safety and/or assessment of efficacy.
- •Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR result before enrollment; those who are PCR positive will be excluded.
- •Major surgical procedure or open surgical biopsy within 28 days of first dose of study drug
- •Active central nervous system (CNS) disease involvement, or prior history of NCI CTCAE Grade ≥3 drug-related CNS toxicity. Subject with known CNS metastases that are treated and stable (without evidence of CNS toxicity) and are not requiring systemic steroids are allowed to be enrolled.
- •Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- •Myocardial infarction within 12 months of screening
- •Use of any other concurrent investigational agents or anticancer agents, excluding hormonal therapy for breast or prostate cancer
- •Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BTX- A51, breastfeeding should be discontinued if the mother is treated with BTX-A
- •Inability to swallow pills or inadequate GI absorption in the opinion of the treating investigator.
研究组 & 干预措施
BTX-A51 21mg
Participants will be enrolled and will complete study procedures as follows:
- Baseline visit with tumor biopsy.
- Tumor biopsy at the end of Cycle 1.
- Radiologic imaging every 2 cycles.
- Cycle 1 through End of Treatment:
--Day 1 of 28 day cycle: Predetermined dose of BTX-A51 3x weekly.
- End of Treatment visit with radiologic imaging.
- Follow-up: every 3 months for 1 year.
干预措施: BTX-A51 (Drug)
BTX-A51 30mg
Participants will be enrolled and will complete study procedures as follows:
- Baseline visit with tumor biopsy.
- Tumor biopsy at the end of Cycle 1.
- Radiologic imaging every 2 cycles.
- Cycle 1 through End of Treatment:
--Day 1 of 28 day cycle: Predetermined dose of BTX-A51 3x weekly.
- End of Treatment visit with radiologic imaging.
- Follow-up: every 3 months for 1 year.
干预措施: BTX-A51 (Drug)
结局指标
主要结局
Number of participants with adverse events, with laboratory abnormalities, with dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event
时间窗: All AEs will be recorded from the time the subject signs informed consent until 30 days after the last dose of study BTX-A51.
Safety and tolerability will be monitored through continuous reporting of treatment-emergent and treatment-related adverse events, laboratory abnormalities, and incidence of subjects experiencing dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event. Toxicities are to be assessed according to the CTCAEv5.
次要结局
- Overall Response Rate (ORR)(ORR expected to be observed up to 3 years)
- 1-year Progression-Free Survival (PFS) Rate(1 year)
- 1-year Overall Survival (OS)(1 year)
研究者
Michael Wagner, MD
Sponsor Investigator
Dana-Farber Cancer Institute