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

NCT ID: NCT03130790

Last Updated: 2022-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-31
• Study Completion Date: 2019-02-22

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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Varlititib+mFOLFOX6

Group Type: EXPERIMENTAL

Varlitinib

Intervention Type: DRUG

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

mFOLFOX6

Intervention Type: 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.

Placebo+mFOLFOX6

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

mFOLFOX6

Intervention Type: 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.

Interventions

Varlitinib

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

Intervention Type: DRUG

mFOLFOX6

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

mFOLFOX6

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.

Intervention Type: DRUG

Other Intervention Names

ASLAN001; ARRY-334543; SPS4370; QBT01

Eligibility Criteria

Inclusion Criteria

1. Subjects of respective country's legal age or older at the time of written informed consent.

2. 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.

3. 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

4. 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.

5. Have radiographically measurable disease as defined by RECIST v1.1

6. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

7. Estimated life expectancy of more than 4 months

8. Able to swallow and retain oral medication

9. 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

10. 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

11. Willingness to use highly effective birth control method (failure rate <1%) while on study.

1. Subjects of respective country's legal age or older at the time of written informed consent.

2. 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.

3. 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.

4. 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*.

5. Note: *For details of contraindication related to trastuzumab, refer to package insert or US treatment guideline

6. Subjects with ECOG performance status of 0 to 1

7. Able to swallow and retain oral medication

8. Subject with adequate organ and hematological function:

a) 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).

b) Renal functions, as follows: i. Serum creatinine ≤ 1.5x ULN or eGFR> 60 mL/min/1.73m2 c) 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

9. 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

10. Willingness to use highly effective birth control method (failure rate <1%) while on study.

Exclusion Criteria

1. 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.

2. 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.

3. Subjects have undergone major surgery within 28 days prior to randomization

4. Subject with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 4weeks).

5. 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.

6. 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.

7. 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).

8. Female subjects who are pregnant or breast feeding.

9. Subjects who were previously treated with varlitinib.

10. Subjects who took other investigational drugs and/or used investigational medical devices or have undergone major surgery within 28 days before initiating varlitinib therapy.

11. Are currently on or have received anti-cancer therapy, radiation or local treatment within the past 28 days

12. 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)

13. 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).

14. Known history of drug addiction within the past 1 year.

15. Subjects who need continuous treatment with proton pump inhibitors during the study period.

16. 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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ASLAN Pharmaceuticals

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

2 Sites

Tallinn, , Estonia

1 Site

Hong Kong, , Hong Kong

2 Sites

Kaunas, , Lithuania

1 Site

Vilnius, , Lithuania

2 Sites

Kuala Lumpur, , Malaysia

1 Site

Singapore, , Singapore

2 Sites

Daegu, , South Korea

1 Site

Incheon, , South Korea

1 Site

Jeongnam, , South Korea

11 Sites

Seoul, , South Korea

2 Sites

Suwon, , South Korea

1 Site

Kaohsiung City, , Taiwan

1 Site

Taichung, , Taiwan

1 Site

Taipei, , Taiwan

1 Site

Khon Kaen, , Thailand

1 Site

Pathum Thani, , Thailand

Countries

Estonia; Hong Kong; Lithuania; Malaysia; Singapore; South Korea; Taiwan; Thailand

Other Identifiers

ASLAN001-012

Identifier Type: -

Identifier Source: org_study_id