First in Human Phase 1 Study of AOH1996 in Patients With Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 92
- 试验地点
- 5
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
This phase I trial studies the side effects and best dose of AOH1996 in treating patients with solid tumors that do not respond to treatment (refractory). AOH1996 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of AOH1996.
II. To establish the recommended phase 2 dose of AOH1996.
III. To establish the recommended phase 2 dose of AOH1996 when given in conjunction with a TKI for NSCLC.
SECONDARY OBJECTIVES:
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
- •Informed Consent and Willingness to Participate
- •1. Documented informed consent by the participant
- •2. Willingness to permit study team to obtain and use archival tissue, if already existing
- •Age Criteria, Performance Status and Life Expectancy
- •3. Age: ≥ 18 years
- •4. ECOG performance status ≤ 2
- •5. Life expectancy of > 3 months
- •Nature of Illness and Treatment History __
- •Patients with solid tumors failing standard therapies or patients refusing standard treatments (exception: Part B NSCLC combination (EGFR TKI + AOH1996) cohort: patients with stable disease or better on EGFR TKI for at least 2 months)
- •Contraception
- •Agreement by females and males of childbearing potential* to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication. See Appendix B for guidelines.
- •- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
- •Laboratory Criteria (to be performed within 14 days prior to Day 1)
- •8. ANC ≥ 1,500/mm3
- •9. Platelets ≥ 100,000/mm3 :
- •10. Total serum bilirubin ≤ 1.5 x ULN
- •11. AST =< 1.5 x ULN or =< 3 x ULN with liver metastases
- •12. ALT =< 1.5 x ULN or =< 3 x ULN with liver metastases
- •13. Creatinine clearance of ≥ 60 mL/min per 24 hour urine or the Cockcroft-Gault
- •14. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
排除标准
- •Concomitant Medications/Therapies __
- •Dietary/herbal supplements
- •2. Other investigational products or chemotherapy. Exception: EGFR TKI in the NSCLC expansion cohort is allowed.
- •3. Warfarin
- •4. Current or planned use of agents contraindicated for use with strong CYP3A4 inducers
- •5. Strong inhibitors or inducers of CYP2C9
- •6. Strong inhibitors or inducers of CYP3A
- •Other Illnesses and Conditions
- •7. Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting).
- •8. Women who are or are planning to become pregnant or breastfeed
- •9. Known allergy to any of the components within the study agents and/or their excipients.
- •10. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
- •11. Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution/recovery is deemed adequate by the investigator (e.g. recovery from major surgery, completion of treatment for severe infection).
- •Noncompliance
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
- •**Eligibility should be confirmed per institutional policies.
研究组 & 干预措施
Treatment (PCNA inhibitor AOH1996)
Patients receive PCNA inhibitor AOH1996 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: PCNA Inhibitor AOH1996 (Drug)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: Up to 30 days after last study drug is given
Toxicity and adverse events will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All toxicities/AEs will be recorded from the initiation of protocol therapy through the follow-up period.
Dose limiting toxicities
时间窗: Up to 28 days (cycle 1)
Toxicities will be graded according to NCI CTCAE version 4.0.
次要结局
- Response rate(Up to 2 years)
- Time to treatment failure(Assessed up to 2 years)
- Progression-free survival(Assessed up to 2 years)
- Overall survival(Assessed up to 2 years)