Varlitinib in Combination With mFOLFOX6 for Advanced or Metastatic Gastric Cancer (First Line)

NCT03130790 | Completed Phase 2

• 1 other identifier: ASLAN001-012
• Study Type: interventional
• Target: 52
• Locations: 8 countries
• Sites: 16

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage change from baseline in tumor size at Week 12 - Phase 2 part

  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

  At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 3 months)

• Overall Survival (OS) - Phase 3 part

  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.

  When 247 OS events have occured. 247 OS is estimated to occur after approximately 45 months

Secondary Outcomes (20)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (2)

Varlititib+mFOLFOX6

EXPERIMENTAL

Drug: Varlitinib; Drug: mFOLFOX6

Placebo+mFOLFOX6

PLACEBO COMPARATOR

Drug: Placebo; Drug: mFOLFOX6

Interventions

Varlitinib DRUG

300mg, oral tablets, twice daily for 2 weeks. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Also known as: ASLAN001, ARRY-334543, SPS4370, QBT01

Varlititib+mFOLFOX6

mFOLFOX6 DRUG

concurrent oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 IV in 500 ml 5% dextrose water (D5W) over 120 minutes on Day 1; then 5 Fluorouracil bolus 400 mg/m2 IV on Day 1 followed by continuous infusion 2400 mg/ m2 over 46 hours starting on Day 1) every 2 weeks. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Varlititib+mFOLFOX6

Placebo DRUG

oral tablets, twice daily for 2 weeks. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo+mFOLFOX6

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects of respective country's legal age or older at the time of written informed consent.
• Subjects with histologically confirmed inoperable locally advanced, recurrent, or metastatic adenocarcinoma of the stomach or GEJ cancers may include Siewert Class I, II, or III types.
• Mandatory provision of an unstained, archived tumor tissue sample in a quantity sufficient to allow for local lab analysis of HER1 and HER2 expression status. If archived tumor tissue is not available, subject must agree to undergo fresh core biopsy to obtain adequate tumor tissue
• Subjects with tumors with IHC evidence of expression of HER1 (at level of + or ++ or +++) and HER-2 (at level of +, or ++) using standard criteria in the local lab. Subjects with HER-2 over expression at level of +++ determined by IHC and subject confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by FISH but has contradiction to trastuzumab\*.
• \*For details of contraindication related to trastuzumab, refer to package insert or US treatment guideline.
• Have radiographically measurable disease as defined by RECIST v1.1
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Estimated life expectancy of more than 4 months
• Able to swallow and retain oral medication
• Subject with adequate organ and hematological function:
• d) Hematological function, as follows: i. Absolute neutrophil count (ANC) ≥1.5 x 109/L ii. Platelet count ≥ 100 x 109/L iii. HgB≥9 g/dL (packed red cell blood transfusions are not allowed within one week prior to baseline hematology profile).
• e) Renal functions, as follows: i. Serum creatinine ≤1.5x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR)\> 60 mL/min/1.73m2 f) Hepatic function, as follows: i. Total bilirubin ≤1.5 x ULN ii. AST and ALT ≤2.5 x ULN (or ≤5 x ULN in subjects with liver metastasis) iii. Albumin ≥25 g/L
• Negative serum human chorionic gonadotropin (HCG)/ or urine pregnancy test within 7 days prior to randomization for premenopausal women of reproductive capacity and for women 12 months after menopause
• Willingness to use highly effective birth control method (failure rate \<1%) while on study.
• Subjects of respective country's legal age or older at the time of written informed consent.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ASLAN Pharmaceuticals: lead

Study Sites (16)

2 Sites

Tallinn, Estonia

Location

1 Site

Hong Kong, Hong Kong

Location

2 Sites

Kaunas, Lithuania

Location

1 Site

Vilnius, Lithuania

Location

2 Sites

Kuala Lumpur, Malaysia

Location

1 Site

Singapore, Singapore

Location

2 Sites

Daegu, South Korea

Location

1 Site

Incheon, South Korea

Location

1 Site

Jeongnam, South Korea

Location

11 Sites

Seoul, South Korea

Location

2 Sites

Suwon, South Korea

Location

1 Site

Kaohsiung City, Taiwan

Location

1 Site

Taichung, Taiwan

Location

1 Site

Taipei, Taiwan

Location

1 Site

Khon Kaen, Thailand

Location

1 Site

Pathum Thani, Thailand

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

ARRY-334543

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2017
• First Posted: April 26, 2017
• Study Start: August 31, 2017
• Primary Completion: December 20, 2018
• Study Completion: February 22, 2019
• Last Updated: February 15, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); MY (1); TW (3); SG (1); HK (1); LI (2); KR (5); TH (2)