A Phase II, Open Label, Multi-center, Multi-arm Study of Ceritinib in Patients With Advanced Solid Tumors and Hematological Malignancies Characterized by Genetic Abnormalities of Anaplastic Lymphoma Kinase (ALK)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment
研究概览
简要总结
This is Proof-of-Concept (POC) study to assess the preliminary antitumor activity and safety and tolerablity using ceritinib (LDK378) in the treatment of life threatening tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases).
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
- •Patient has a histologically or cytologically confirmed diagnosis of ALK positive (ALK+) tumor other than Non-Small Cell Lung Cancer (NSCLC).
- •Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory.
- •Patient has WHO Performance Status (PS) ≤ 2
- •Patient must have received at least one line of prior systemic treatment for recurrent, locally advanced and/or metastatic disease, and may have discontinued for:
- •Disease progression as defined by RECIST 1.1 for solid tumors; by RANO for GBM and by Cheson assessment criteria for lymphoma, or
- •Intolerance described as any discontinuation due to an AE of any grade despite appropriate supportive treatment
- •Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
- •Patient has received no chemotherapy, immunotherapy or stem cell therapy at least 4 weeks before starting ceritinib
- •Radiotherapy and prior ALK inhibitors must be stopped at least 1 week prior to starting ceritinib
- •Recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology Criteria for Adverse Events [CTCAE] v4.03).
排除标准
- •Patient has ALK+lung cancer
- •Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
- •Patient with acute or chronic GI disease that may significantly alter the absorption of ceritinib.
- •Patient with a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
- •Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
- •Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months).
- •Patient has evidence of active viral hepatitis, including Hepatitis A, B or C (testing for viral hepatitis is not mandatory).
- •Patient has known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
研究组 & 干预措施
Inflammatory myofibroblastic tumor (IMT)
Patients diagnosed with IMT with a confirmed translocation involving the ALK gene
干预措施: Ceritinib (LDK378) (Drug)
Anaplastic large cell lymphoma (ALCL)
Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive
干预措施: Ceritinib (LDK378) (Drug)
Glioblastoma (GBM)
Patients with GBM with a translocation involving the ALK gene
干预措施: Ceritinib (LDK378) (Drug)
Any other ALK-positive tumor
Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2).
干预措施: Ceritinib (LDK378) (Drug)
结局指标
主要结局
Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment
时间窗: Baseline up to approximately 16 weeks
The DCR is defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks from the start of ceritinib treatment. The assessment criteria are: Solid Tumors (RECIST 1.1., Response Evaluation Criteria in Solid Tumors); GBM (RECIST 1.1 and RANO, Response Evaluation in Neuro-Oncology); Hematologic tumors (Cheson).
次要结局
- Overall Response Rate (ORR) Per Investigator Assessment(Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks)
- Duration of Response (DOR) Per Investigator Assessment(Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks)
- Time to Response (TTR) Per Investigator Assessment(Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks)
- Progression Free Survival (PFS) Per Investigator Assessments(Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks)
- Percent of Participant Deaths During Treatment and Follow-up(Baseline up to approximately 84 weeks)