NCT03129074撤回2 期
A Phase 2, Single Arm Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as First-line Systemic Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of the study is to assess the efficacy of varlitinib in combination with capecitabine as measured by objective response rate (ORR) assessed by independent central review (ICR), based on RECIST v1.1 criteria.
详细描述
Also to explore the role of biomarkers as predictors of response and clinical benefit with varlitinib
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
- •Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.
- •Are able to understand and willing to sign the informed consent form.
- •Have histologically confirmed diagnoses of relapsed, locally advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and carcinoma of Ampulla of Vater.
- •Have eligible tumor tissue (archival or fresh) for the evaluation of relevant primary endpoints.
- •(Note: For patients without eligible tumor tissue, a discussion with the sponsor is mandatory).
- •Have radiographically measurable disease as determined by the investigator based on the RECIST v1.1 criteria.
- •Have no evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN).
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Have an estimated life expectancy of more than 3 months, at the time of screening.
- •Have adequate organ and hematological function:
- •Hematological function, as follows:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •Platelet count ≥ 100 x 109/L
- •Renal functions, as follows:
- •estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) > 50 mL/min/1.73m2
- •Hepatic function, as follows:
- •Total bilirubin ≤ 1.5 x ULN
- •aspartate aminotransferase and alanine aminotransferase ≤ 5 x ULN
排除标准
- •Have received systemic anti-cancer treatment except (neo-) adjuvant therapy for early stage disease.
- •Are currently on or have received radiation or local treatment within the past 4 weeks for the target lesion(s), prior to screening.
- •Had undergone major surgical procedures within 28 days prior to study cycle 1 day
- •Have a metastatic brain lesion(s), including asymptomatic and well controlled lesion(s).
- •Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, or difficulty in swallowing and retaining oral medications.
- •Have any history of other malignancy unless in remission for more than 1 year (skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
- •Are female patients who are pregnant or breast feeding.
- •Have been previously treated with varlitinib or capecitabine.
- •Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication.
- •Have unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior anti-cancer treatment.
- •Have a known positive test for human immunodeficiency virus, active viral hepatitis C, viral hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL.
- •Have a known history of drug addiction within last 1 year, on the basis of which there could be a higher risk of non-compliance to study treatment.
- •Need continuous treatment with proton pump inhibitors during the study period.
- •Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or with a history of interstitial lung disease or current interstitial lung disease.
- •Have any history or presence of clinically significant condition which in the opinion of the investigator could jeopardize the safety of the patient or the validity of the study results.
- •Have a baseline corrected QT interval > 450 ms or patients with known long QT syndrome, torsade de pointes, symptomatic ventricular tachycardia, unstable cardiac syndrome in the past 3 months before screening visit, > class 2 NYHA (The New York Heart Association Functional Classification heart failure), > grade 2 CCS (the Canadian Cardiovascular Society Guidelines) angina pectoris, or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, or sotalol methadone.
研究组 & 干预措施
Varlitinib given in combination with capecitabine
Experimental
- PO varlitinib 300 mg BID
- PO capecitabine 1000 mg/m2 BID
干预措施: Varlitinib (Drug)
Varlitinib given in combination with capecitabine
Experimental
- PO varlitinib 300 mg BID
- PO capecitabine 1000 mg/m2 BID
干预措施: Capecitabine (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Through study duration, estimated 3 years
Number (%) of patients with at least one visit response of CR or PR. Tumor evaluations will continue until the earlier of disease progression or starting a subsequent anti-cancer therapy.
Biomarker
时间窗: Through study duration, estimated 3 years
Use Next generation sequencing/Immunohistochemistry to identify relationships between response to varlitinib and mutations or overexpression in human epidermal growth factor receptor (HER) receptors and the downstream signaling proteins, as well as, mutations in selected cancer pathways.
次要结局
- Progression-free survival (PFS)(Through study duration, estimated 3 years)
- Overall survival (OS)(Through study duration, estimated 3 years)
- Duration of response (DoR)(Through study duration, estimated 3 years)
- Disease control rate (DCR)(Through study duration, estimated 3 years)
- Incidence of Adverse Events and changes from baseline in safety parameters(Through study duration, estimated 3 years)
- Objective response rate (ORR)(Through study duration, estimated 3 years)
研究者
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