Open-label, Multicentre, Phase Ib/II Study of MEN1611, a PI3K Inhibitor, and Cetuximab in Patients With PIK3CA Mutated Metastatic Colorectal Cancer Failing Irinotecan, Oxaliplatin, 5-FU and Anti-EGFR Containing Regimens
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 28
- 主要终点
- Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab
研究概览
简要总结
Open-label, dose-confirmation and cohort expansion, multicenter, Phase Ib/II study to assess the anti-tumor activity and safety of MEN1611 in combination with cetuximab for the treatment of participants with phosphatidylinositol 3-kinase, catalytic, alpha polypeptide gene (PIK3CA)-mutated metastatic colorectal cancer.
详细描述
This Phase Ib/II study investigated the anti-tumor activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male participants affected by PIK3CA-mutated, neuroblastoma-Kristen-rat sarcoma virus (N-K-RAS) wild-type, and BRAF wild-type metastatic colorectal cancer.
MEN1611 is a potent, selective class I phosphoinositide 3-kinase (PI3K) inhibitor. The maximum tolerated dose of MEN1611 given as single agent was assessed in a Phase I trial in participants with advanced solid tumors.
This Phase Ib/II started with a dose confirmation part (Step 1) to identify the recommended phase 2 dose of MEN1611 given in combination with cetuximab.
The study continued with a cohort expansion (Step 2) to explore the anti-tumor activity of the selected MEN1611 dose level combined with cetuximab with further assessment of safety and tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Histological documentation of adenocarcinoma of the colon or rectum.
- •Progression or recurrence following prior irinotecan, oxaliplatin, 5-fluorouracil (5-FU) and anti-epidermal growth factor receptor (EGFR) containing regimens for metastatic disease.
- •Best response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria to the last anti-EGFR containing regimen of partial response or stable disease for at least 4 months.
- •Measurable disease according to RECIST criteria.
- •N-K-RAS (exons 2, 3 and 4) and BRAF wild-type and PIK3CA mutated.
- •Eastern Cooperative Oncology Group performance status of 0 or
排除标准
- •Previous treatment with PI3K inhibitor.
- •Brain metastases, unless treated >4 weeks before screening visit and only if clinically stable and not receiving corticosteroids.
- •National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 Grade ≥2 diarrhea.
- •History of significant, uncontrolled or active cardiovascular disease.
- •Known active or uncontrolled pulmonary dysfunction.
- •Uncontrolled diabetes mellitus (glycated hemoglobin >7%) and fasting plasma glucose >126 milligrams/deciliter.
- •Known history of human immunodeficiency virus infection or active infection with hepatitis C virus or hepatitis B virus.
- •Concurrent chronic immunosuppressive treatment either with steroids or other immunosuppressive agents.
研究组 & 干预措施
MEN1611
MEN1611 + Cetuximab
干预措施: MEN1611 (Drug)
MEN1611
MEN1611 + Cetuximab
干预措施: Cetuximab (Drug)
结局指标
主要结局
Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab
时间窗: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab
时间窗: Up to 37 Months
The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
Phase 1b: Number of Participants With DLTs for MEN1611
时间窗: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting \>7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.
次要结局
- Plasma Concentration of MEN1611 in Combination With Cetuximab(Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle))
- Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab(Up to 37 Months)
- Duration of Response (DOR) of MEN1611 in Combination With Cetuximab(Up to 37 months)
- Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab(Up to 37 months)
- Overall Survival (OS) of MEN1611 in Combination With Cetuximab(Up to 37 months)