Phase I Trial of ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas
概览
- 阶段
- 1 期
- 干预措施
- ASTX727
- 疾病 / 适应症
- Neurological Cancer
- 发起方
- Massachusetts General Hospital
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose
- 状态
- 招募中
- 最后更新
- 16天前
概览
简要总结
this research study is evaluating the highest dose of ASTX727 that can be administered safely to recurrent/progressive non-enhancing IDH mutant gliomas patients.
详细描述
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied. The FDA (the U.S. Food and Drug Administration) has not approved ASTX727 as a treatment for any disease. ASTX727 is made up of the 2 study drugs cedazuridine and decitabine. Cedazuridine is believed to work by slowing down how fast decitabine is broken down by the body. Decitabine is believed to work by blocking abnormal cells or cancer cells from growing.
研究者
Isabel Arrillaga-Romany
Principal Investigator
Massachusetts General Hospital
入排标准
入选标准
- •Participants must be ≥18 years of age.
- •Participants must have histologically or cytologically confirmed glioma, with documented IDH1 and/or IDH2 gene-mutation.
- •Participants must have radiographic evidence of non-enhancing disease progression/recurrence per RANO criteria for low grade gliomas (LGG).
- •Patients who have received prior treatment with chemotherapy, radiation, or a combination of both are eligible. Also, patients who have not received any prior treatment for their glioma are also eligible.
- •Participants must be ≥12 weeks from completion of radiation.
- •Participants must have a baseline brain MRI scan within 28 days prior to Day 1 of treatment.
- •Participants must be on a stable or decreasing dose of glucocorticoids for 7 days prior to registration.
- •Participants must have archived primary tumor biopsies or surgical specimens for additional exploratory translational studies. At least 100-micron length of FFPE tissue or a tissue block should be available for enrollment and for shipment to the Sponsor, or a laboratory designated by the Principal Investigator. If less material is available, participants could still be eligible after discussion with the Principal Investigator who will assess and confirm that there is sufficient material for key evaluations.
- •Participants must be able to understand and willing to sign an informed consent. A legally authorized representative may consent on behalf of a participant who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site's Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
- •Participants must have KPS ≥ to 70
排除标准
- •Participants with enhancing disease on brain MRI.
- •Participants who received systemic anticancer therapy \<28 days prior to registration. One exception: participants on lomustine/CCNU must wait at least 42 days from last date of drug administration to registration.
- •Participants who received an investigational agent \<14 days prior to registration. In addition, the first dose of ASTX727 should not occur before a period ≥5 half-lives of the investigational agent has elapsed.
- •Participants with prior treatment with bevacizumab (Avastin) are excluded.
- •Participants who are pregnant or breast-feeding.
- •Participants with an active severe infection that requires anti-infective therapy or with an unexplained fever \>38.5°C during screening visits or on their first day of study drug administration.
- •Participants with known additional malignancy that is progressing or requires active treatment within 2 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer that has undergone potentially curative therapy, or surgically treated prostate cancer.
- •Participants with known hypersensitivity to any of the components of ASTX
- •Participants with a history of myocardial infarction within the 6 months prior to screening.
- •Participants with a known history of severe and/or uncontrolled ventricular arrhythmias.
研究组 & 干预措施
ASTX727 (Cedazuridine + Cytidine Antimetabolite Decitabine)
-ASTX727 administered orally for 5 or 6 consecutive days every 28d cycle and will de-escalate to 4 consecutive days every 28 d cycle.
干预措施: ASTX727
Expansion Cohort
* Oral ASTX727 will be administered daily for 4, 5 or 6 consecutive days * Surgical resection will take place 12 days (+/- 1 day) after initiation of treatment
干预措施: ASTX727
结局指标
主要结局
Maximum tolerated dose
时间窗: 1 year
Participants will be enrolled at escalating doses using a standard 3+3 dose escalation design until the maximum administered dose is reached or until dose limiting toxicities result in the end of dose escalation. The maximum tolerated dose is the highest administered dose level at which participants experienced experienced 1 or fewer dose limiting toxicities.
次要结局
- Median Progression Free Survival(From the time of randomization until disease progression or death, up to five years)
- Overall Survival(From the time of randomization until death, up to five years)
- Response Rate(1 Year)