A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Varlitinib Plus Capecitabine Versus Placebo Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as Second Line Systemic Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 21
- 主要终点
- Objective Response Rate (ORR) - Part 1
研究概览
简要总结
This protocol for Varlitinib is developed for the treatment of Biliary Tract Cancer. Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive inhibitor of the tyrosine kinases - epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER4. Varlitinib may be beneficial to subjects with cancer by simultaneous inhibition of these receptors. The purpose of this study is to determine the safety and efficacy of Varlitinib in combination with capecitabine for the treatment of Biliary Tract Cancer. Treatment groups are Varlitinib+capecitabine and Placebo + capecitabine
详细描述
Part 1 of study(Phase 2) is planned to have 120 patients and anticipated completion on July 2019. Recruitment completed.
Part 2 of study(Phase 3) is planned to have 350 patients and anticipated completion on Dec 2022. Not yet recruiting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will be eligible for the study if they:
- •Are of or older than the legal age in the respective countries at the time when written informed consent is obtained
- •Have histologically or cytologically confirmed advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma (CCA), gallbladder cancer and carcinoma of Ampulla of Vater. This includes clinical diagnosis of biliary tract cancer with histological confirmation of adenocarcinoma.
- •Have received and failed one and only one prior line of systemic treatment for advanced or metastatic disease with radiologic evidence of disease progression. This prior line of systemic treatment must also contain gemcitabine
- •Have received at least 6 doses of gemcitabine containing treatment in first line (Adjuvant therapy is not regarded as 1st line therapy)
- •Have radiographically measurable disease based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by Independent Central Review (ICR) (For Part 1)
- •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 or equal to 1.5 × upper level of normal (ULN)
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Are able to understand and willing to sign the informed consent form
- •Have adequate organ and hematological function:
- •Hematological function, as follows:
- •Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- •Platelet count ≥ 100 × 109/L
- •Renal functions, as follows:
- •Estimated glomerular filtration rate or creatinine clearance > 50 mL/min/1.73m2
- •Hepatic function, as follows:
- •Albumin ≥ 3 g/dL
- •Total bilirubin ≤ 1.5 × ULN
- •Aspartate aminotransferase and alanine aminotransferase ≤ 5 × ULN
排除标准
- •Subjects will be ineligible for the study if they:
- •Are currently on or have received anti-cancer therapy within the past 3 weeks before receiving the first dose of study medication
- •Are currently on or have received radiation or local treatment within the past 3 weeks for the target lesion(s) before receiving the first dose of study medication
- •Have evidence of multiple (≥ 2) peritoneal metastases or ascites at baseline as assessed by ICR (For Part 1). (Ascites which can be attributed by non-malignant causes is not excluded. Minimal ascites, which does not require paracentesis is permitted.)
- •Have had major surgical procedures within 14 days prior to first dose of study medication
- •Have a known metastatic brain lesion(s), including asymptomatic and well controlled lesion(s)
- •Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications which in the opinion of the Investigator could jeopardize the validity of the study results
- •Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
- •Have any history of other malignancy unless in remission for more than 1 year (non-melanoma 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 have been previously treated with capecitabine as first line therapy for advanced or metastatic disease. For patients who have previously received capecitabine as a radiosensitizer or as part of their adjuvant therapy and their disease has relapsed for more than 6 months after their last dose of capecitabine adjuvant therapy, their capecitabine therapy will not be considered as a line of systemic chemotherapy for metastatic/advanced disease, and thus they can participate in the study
- •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 (≥ common terminology criteria for adverse events [CTCAE] 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior cancer treatment
- •Have a known positive test for human immunodeficiency virus, hepatitis C (treatment naïve or after treatment without sustained virologic response), or hepatitis B infection with hepatitis B virus deoxyribonucleic acid exceeding 2000 IU/mL
- •Have a known history of drug addiction within last 1 year which, in the opinion of the Investigator, could increase the risk of non-compliance to investigational product
- •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 have a history of interstitial lung disease or current interstitial lung disease
- •Have any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other 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 (Fridericia's formula) (QTcF) > 450 ms or patients with known long QT syndrome; torsade de pointes; symptomatic ventricular tachycardia; an unstable cardiac syndrome in the past 3 months before screening visit; > class 2 New York Heart Association heart failure; or > class 2 angina pectoris; or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, sotalol, or methadone. Please also see prohibited medication/therapy (Section 5.4.10.1)
研究组 & 干预措施
Varlitinib and Capecitabine
干预措施: Varlitinib (Drug)
Varlitinib and Capecitabine
干预措施: Capecitabine (Drug)
Placebo and Capecitabine
干预措施: Capecitabine (Drug)
Placebo and Capecitabine
干预措施: Placebo (for Varlitinib) (Drug)
结局指标
主要结局
Objective Response Rate (ORR) - Part 1
时间窗: Data obtained up until progression, or until last evaluable assessment in the absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.
Part 1: The ORR was defined as the number (%) of subjects with ≥ 1 visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or until last evaluable assessment in the absence of progression, was included in the assessment of ORR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. Best overall RECIST Response (BOR) was calculated based on the overall visit responses from each RECIST assessment, i.e. the best response a subject had following randomization and prior to RECIST progression or the last evaluable assessment in the absence of RECIST progression. Categorization of BOR was based on the RECIST criteria using the following response categories: CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE).
Progression-free Survival (PFS) - Part 1
时间窗: Time from randomization until date of objective disease progression or death (by any cause in absence of disease progression) regardless of whether subject withdrew from randomized therapy or received another antitumor therapy prior to PD, up to 2 years.
Part 1: Progression-free survival (PFS) was defined as the time from randomization (or starting treatment for the Safety Lead-in) until the date of objective disease progression or death (by any cause in the absence of disease progression) regardless of whether the subject withdrew from randomized therapy or received another antitumor therapy prior to disease progression. Subjects who did not experience disease progression or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. However, if the patient progressed or died after ≥ 2 missed visits (12 weeks ± 5 days maximum), the subject was censored at the time of the latest evaluable RECIST assessment. The PFS time was based on the scan/assessment dates rather than visit dates.
次要结局
- Overall Survival (OS) - Part 1(Time from the date of randomization until death due to any cause, up to 2 years)
- Overall Survival (OS) - Safety Lead-In(Time from the date of randomization until death due to any cause, up to 2 years)
- Duration of Response (DoR) - Part 1(Time from the date of first documented response until the date of documented PD or death in the absence of disease progression, up to 2 years)
- Disease Control Rate DCR - Part 1(Number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization.)
- Tumor Size - Part 1(Week 12)
- Number of Participants With Clinically Significant Laboratory Tests- Safety Lead-in(Subject screening visit to 28 days post last study drug administration)
- Number of Participants With Clinically Significant Laboratory Tests - Part 1(Subject screening visit to 28 days post last study drug administration)
- Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Safety Lead-In(Subject screening visit to 28 days post last study drug administration)
- Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Part 1(Subject screening visit to 28 days post last study drug administration)
- Number of Participants With ECG Parameters of Interest - Safety Lead-In(Subject screening visit to 28 days post last study drug administration)
- Number of Participants With ECG Parameters of Interest - Part 1(Subject screening visit to 28 days post last study drug administration)
- ECOG Performance Status - Part 1(Subject screening visit to 28 days post last study drug administration)
- Object Response Rates (ORR) - Safety Lead-In(Data obtained up until progression, or until last evaluable assessment in absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.)