NCT03562832已完成2 期
Phase II, Open Label Clinical Study to Investigate Anti-tumour Effect and Tolerability of the PARP Inhibitor 2X-121 in Patients With Metastatic Breast Cancer Selected by the 2X-121 DRP
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Anti-tumour efficacy after treatment with 600 mg 2X-121 as single oral agent in a 21-days cycle in mBC patients selected by the 2X-121 DRP
研究概览
简要总结
2X-121 is a small molecule targeted inhibitor of Poly ADP ribose polymerase (PARP), a key enzyme involved in DNA damage repair in cancer cells. The PARP inhibitor demonstrated clinical activity in a prior Phase 1 study in a number of solid tumors. 2X-121 has a novel dual-inhibitory action against both PARP 1/2 and Tankyrase 1/2. The molecule is also active in P-glycoprotein expressing cells, suggesting it may overcome some of the PARP inhibitor resistance.
The Phase 2 study is using 2x-121 DRP® biomarker in metastatic breast cancer patients to identify patients likely to respond to and benefit from treatment with 2X-121.
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
- •Signed informed consent form.
- •Age 18 years or older.
- •Histologically or cytological documented mBC (independent of hormone receptor, HER2 status and BRCA1 or 2 status) relapsed in 2 or more different prior therapies.
- •Measurable disease by CT scan or MRI.
- •With a drug response prediction (DRP) for 2X-121 with an outcome measured as being in the upper 20% likelihood of response.
- •Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed.
- •Performance status of ECOG <= 1
- •Recovered to Grade 1 or less from prior surgery or from acute toxicities of prior radiotherapy, or from treatment with cytotoxic, hormonal or biologic agents).
- •>= 2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF.
- •Patients with intracranial disease must be on stable or decreased level of steroid therapy (e.g. dexamethasone) for at least 7 days prior to baseline MRI. Non-enzymatic inducing ant-epileptic drugs are allowed.
- •Adequate conditions as evidenced by the following clinical laboratory values:
- •Absolute neutrophils count (ANC) >= 1.5 x 10E9/L
- •Haemoglobin is at least 4.6 mmol/L
- •Platelets >= 100 x 10E9 /L
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN*
- •Serum bilirubin <= 1.5 ULN
- •Alkaline phosphatase <= 2.5 x ULN*
- •Creatinine <= 1.5 ULN
- •Blood urea within normal limits
- •Creatinine clearance within normal limits. *In case of known liver metastases with ALT and AST <= 5 x ULN and/or alkaline phosphatase <= 5 x ULN. Patients who do not conform to the transaminase and/or alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase and/or alkaline phosphatase levels are considered elevated due to other reasons than deteriorated lever capacity, may be considered for inclusion based on conferred agreement between PI and sponsor.
- •Life expectancy equal or longer than 3 months.
- •Sexually active females of child-producing potential must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.
排除标准
- •- Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period.
- •Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study.
- •Previous treatment with PARP inhibitors
- •Any active infection requiring parenteral or oral antibiotic treatment.
- •Has known HIV positivity.
- •Has known active hepatitis B or C.
- •Has clinical significant (i.e. active) cardiovascular disease:
- •Stroke within <= 6 months prior to day 1
- •Transient ischemic attach (TIA) within <= 6 months prior to day 1
- •Myocardial infarction within <= 6 months prior to day 1
- •Unstable angina
- •New York Hart Association (NYHA) Grade II or greater congestive heart failure (CHF)
- •Serious cardiac arrhythmia requiring medication
- •Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.
- •Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results
- •Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of 2X-
- •Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
- •Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry)
研究组 & 干预措施
PARP inhibitor 2X-121
Experimental
600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients
干预措施: PARP inhibitor 2X-121 (Drug)
结局指标
主要结局
Anti-tumour efficacy after treatment with 600 mg 2X-121 as single oral agent in a 21-days cycle in mBC patients selected by the 2X-121 DRP
时间窗: one year
Overall tumor response according to RECIST
次要结局
- Progression free survival (PFS) after administration of 2X-121 in patients with mBC(one year)
- Duration of objective response after administration of 2X-121 in patients with mBC(one year)
- Overall survival (OS) after administration of 2X-121 in patients with mBC(one year)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(one year)
- Performance status (ECOG)(one year)
研究者
研究点 (2)
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