Varlitinib in Combination With mFOLFOX6 for Advanced or Metastatic Gastric Cancer (First Line)
- Registration Number
- NCT03130790
- Lead Sponsor
- ASLAN Pharmaceuticals
- Brief Summary
This protocol for Varlitinib is developed for the treatment of Gastric 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 mFOLFOX6 for the treatment of Gastric Cancer. Treatment groups are Varlitinib+mFOLFOX6 and Placebo+mFOLFOX6.
- Detailed Description
Phase 2 is planned to recruit approximately 50 or more eligible subjects in order to obtain data from 40 evaluable patients. Anticipated completion date in Dec 2018. Recruitment completed.
Phase 3 is planned to recruit 350 patients. Anticipated completion date in Dec 2022. Not yet recruiting.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
Not provided
- Subject with HER-2 over expression at level of +++ determined by IHC or subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by Fluorescence in situ hybridization (FISH) in the central lab.
- Prior systemic anti-cancer treatment for inoperable locally advanced, recurrent, or metastatic adenocarcinoma of the stomach or GEJ. However, previous neo adjuvant chemotherapy is allowed if subject has progression of disease more than 6 months after neoadjuvant treatment.
- Subjects have undergone major surgery within 28 days prior to randomization
- Subject with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 4weeks).
- Subject with malabsorption syndrome, diseases significantly affecting gastrointestinal function, extensive resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
- Subjects with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, New York heart Association class III or IV congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
- Subjects with any history of other malignancy unless in remission for more than 1 year. (Nonmelanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
- Female subjects who are pregnant or breast feeding.
- Subjects who were previously treated with varlitinib.
- Subjects who took other investigational drugs and/or used investigational medical devices or have undergone major surgery within 28 days before initiating varlitinib therapy.
- Are currently on or have received anti-cancer therapy, radiation or local treatment within the past 28 days
- Subject with unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment(excluding hair loss)
- Subjects with a known history of human immunodeficiency virus (HIV), decompensated cirrhosis, hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL or hepatitis C (treatment naïve or after treatment without sustained virologic response).
- Known history of drug addiction within the past 1 year.
- Subjects who need continuous treatment with proton pump inhibitors during the study period.
- 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 subject or the validity of the study results.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo+mFOLFOX6 Placebo - Placebo+mFOLFOX6 mFOLFOX6 - Varlititib+mFOLFOX6 mFOLFOX6 - Varlititib+mFOLFOX6 Varlitinib -
- Primary Outcome Measures
Name Time Method Percentage change from baseline in tumor size at Week 12 - Phase 2 part At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 3 months) Phase 2 part: Percentage change in tumour size defined as the percentage change from baseline in the sum of longest diameters of target lesions as assessed by ICR and defined by the RECIST v1.1 criteria
Overall Survival (OS) - Phase 3 part When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months Phase 3 part: Overall Survival (OS) defined as the time from randomization until death by any cause. Any subject not known to have died at the time of the analysis will be censored based on the last recorded date on which the subject was known to be alive.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic: accumulation ratio for Cmax (Rac Cmax) - Phase 2 part Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15 Phase 2 part: Pharmacokinetic of Varlitinib
Progression-free survival (PFS) - Phase 3 part When 247 Overall Survival (OS) events have occured (up to approximately 45 months) Phase 3 part: Progression-free survival (PFS) defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of disease progression), whichever comes first. Progression is defined in accordance with the RECIST v1.1 criteria.
Time to response (TTR) - Phase 3 part When 247 Overall Survival (OS) events have occured (up to approximately 45 months) Phase 3 part: Time to response (TTR) defined as the time between date of randomization and first documented response (CR or PR), in the subset of subjects classified as responders in the assessment of ORR.
Pharmacokinetic: maximum observed plasma concentration (Cmax) - Phase 2 part Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15 Phase 2 part: Pharmacokinetic of Varlitinib
Pharmacokinetic: accumulation ratio for AUC (Rac AUC0-6) - Phase 2 part Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15 Phase 2 part: Pharmacokinetic of Varlitinib
Progression-free survival (PFS) - Phase 2 part At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months) Phase 2 part: Progression-free survival (PFS) defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of disease progression), whichever comes first. Progression is defined in accordance with the RECIST v1.1 criteria.
Overall Survival (OS) - Phase 2 part From randomization to end of study (Last subject last visit (LSLV)) (up to approximately 24 months) Phase 2 part: Overall Survival (OS) defined as the time from randomization until death by any cause. Any subject not known to have died at the time of the analysis will be censored based on the last recorded date on which the subject was known to be alive.
Objective Response Rate (ORR) - Phase 3 part When 247 Overall Survival (OS) events have occured (up to approximately 45 months) Phase 3 part: Objective Response Rate (ORR) defined as the proportion of subjects with a best objective response (BOR) of complete response (CR) or partial response (PR), as defined by the RECIST v1.1 criteria.
Health-related quality of life (QoL) - Phase 3 part When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months QLQ-C30 and EORTC QLQ-STO22 questionnaire
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Gastric Cancer 22 items (EORTC QLQ STO22) measuring patients general cancer symptoms and functioning - Phase 3 part When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months Phase 3 part: To assess on disease-related symptoms and health-related quality of life (QoL) of gastric cancer patients
Objective Response Rate (ORR) - Phase 2 part At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months) Phase 2 part: Objective Response Rate (ORR) defined as the proportion of subjects with a best objective response (BOR) of complete response (CR) or partial response (PR), as defined by the RECIST v1.1 criteria.
Time to response (TTR) - Phase 2 part At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months) Phase 2 part: Time to response (TTR) defined as the time between date of randomization and first documented response (CR or PR), in the subset of subjects classified as responders in the assessment of ORR.
Duration of Response (DoR) - Phase 2 part At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months) Phase 2 part: Duration of Response (DoR) defined as the time, in days, from the first recorded achievement of a response (PR or above) until time of objective disease progression in the subset of subjects classified as responders in the assessment of ORR.
Disease Control Rate (DCR) - Phase 2 part At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 12 months) Phase 2 part: Disease Control Rate (DCR) defined as the proportion of subjects with a (BOR of CR or PR, or SD maintained for a minimum of twelve weeks (-5 days) from randomization, as defined by the RECIST v1.1 criteria.
Pharmacokinetic: area under the plasma concentration time curve (AUC) from 0 to 6 hours (AUC0-6) - Phase 2 part Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15 Phase 2 part: Pharmacokinetic of Varlitinib
Pharmacokinetic: time to Cmax (tmax) - Phase 2 part Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15 Phase 2 part: Pharmacokinetic of Varlitinib
Disease Control Rate (DCR) - Phase 3 part When 247 Overall Survival (OS) events have occured (up to approximately 45 months) Phase 3 part: Disease Control Rate (DCR) defined as the proportion of subjects with a (BOR of CR or PR, or SD maintained for a minimum of twelve weeks (-5 days) from randomization, as defined by the RECIST v1.1 criteria.
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30) measuring patients general cancer symptoms and functioning - Phase 3 part When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months Phase 3 part: To assess on disease-related symptoms and health-related quality of life (QoL) of gastric cancer patients
Duration of Response (DoR) - Phase 3 part When 247 Overall Survival (OS) events have occured (up to approximately 45 months) Phase 3 part: Duration of Response (DoR) defined as the time, in days, from the first recorded achievement of a response (PR or above) until time of objective disease progression in the subset of subjects classified as responders in the assessment of ORR.
Incidence of Adverse Events (AEs) - Phase 3 part When 247 Overall Survival (OS) events have occured (up to approximately 45 months) Phase 3 part: Incidence of AEs, categorized in accordance to CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests)
Trial Locations
- Locations (3)
11 Sites
🇰🇷Seoul, Korea, Republic of
1 Site
🇹🇭Pathum Thani, Thailand
2 Sites
🇲🇾Kuala Lumpur, Malaysia