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Gastric CancerPhase 2/3NCT03130790

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

A Phase 2/3 study testing Varlitinib and mFOLFOX6 in people with Gastric Cancer, run by ASLAN Pharmaceuticals at 16 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
Conditions the study is for
Gastric Cancer
What is being tested?
Varlitinib and mFOLFOX6
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
16 sitesin 8 countries
Study dates
31 Aug 2017to 22 Feb 2019
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • 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).
  • 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.
  • 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*.
  • Note: *For details of contraindication related to trastuzumab, refer to package insert or US treatment guideline
  • Subjects with ECOG performance status of 0 to 1
  • Able to swallow and retain oral medication
  • Subject with adequate organ and hematological function:
  • 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).
  • 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
  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

16 sites in 8 countries.

16 sites in 8 countries

South Korea5 sites
  • 2 Sites

    Daegu

  • 1 Site

    Incheon

  • 1 Site

    Jeongnam

  • 11 Sites

    Seoul

  • 2 Sites

    Suwon

Other trials in South Korea

Taiwan3 sites
  • 1 Site

    Kaohsiung City

  • 1 Site

    Taichung

  • 1 Site

    Taipei

Other trials in Taiwan

Lithuania2 sites
  • 2 Sites

    Kaunas

  • 1 Site

    Vilnius

Other trials in Lithuania

Thailand2 sites
  • 1 Site

    Khon Kaen

  • 1 Site

    Pathum Thani

Other trials in Thailand

Estonia1 site
  • 2 Sites

    Tallinn

Other trials in Estonia

Hong Kong1 site
  • 1 Site

    Hong Kong

Other trials in Hong Kong

Malaysia1 site
  • 2 Sites

    Kuala Lumpur

Other trials in Malaysia

Singapore1 site
  • 1 Site

    Singapore

Other trials in Singapore

About this study

Official title: A Two-Part Phase 2/ 3 Multicentre, Double-Blind, Randomized, Placebo Controlled Study of Varlitinib Plus mFOLFOX6 Verses Placebo Plus mFOLFOX6 In Subjects With HER1/ HER2 Co Expressing Advanced or Metastatic Gastric Cancer Without Prior Exposure to Systemic Therapy

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.

Read the 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
Being tested
Varlitinib, mFOLFOX6, Placebo
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VarlitinibDrug

    Also called ASLAN001, ARRY-334543, SPS4370, QBT01

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

  • mFOLFOX6Drug

    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.

  • PlaceboDrug

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

  • mFOLFOX6Drug

    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.

Study groups in NCT03130790
Study groupRoleWhat they receive
Varlititib+mFOLFOX6ExperimentalNot described
Receives: Drug: Varlitinib; Drug: mFOLFOX6
Placebo+mFOLFOX6Placebo comparatorNot described
Receives: Drug: Placebo; Drug: mFOLFOX6

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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.

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

Secondary outcomes (20)
  1. Objective Response Rate (ORR) - Phase 2 part

    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.

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

  2. Progression-free survival (PFS) - Phase 2 part

    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.

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

  3. Time to response (TTR) - Phase 2 part

    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.

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

  4. Duration of Response (DoR) - Phase 2 part

    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.

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

  5. Disease Control Rate (DCR) - Phase 2 part

    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.

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

  6. Overall Survival (OS) - Phase 2 part

    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.

    Measured: From randomization to end of study (Last subject last visit (LSLV)) (up to approximately 24 months)

  7. Pharmacokinetic: area under the plasma concentration time curve (AUC) from 0 to 6 hours (AUC0-6) - Phase 2 part

    Phase 2 part: Pharmacokinetic of Varlitinib

    Measured: Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15

  8. Pharmacokinetic: maximum observed plasma concentration (Cmax) - Phase 2 part

    Phase 2 part: Pharmacokinetic of Varlitinib

    Measured: Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15

  9. Pharmacokinetic: time to Cmax (tmax) - Phase 2 part

    Phase 2 part: Pharmacokinetic of Varlitinib

    Measured: Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15

  10. Pharmacokinetic: accumulation ratio for AUC (Rac AUC0-6) - Phase 2 part

    Phase 2 part: Pharmacokinetic of Varlitinib

    Measured: Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15

  11. Pharmacokinetic: accumulation ratio for Cmax (Rac Cmax) - Phase 2 part

    Phase 2 part: Pharmacokinetic of Varlitinib

    Measured: Pharmacokinetic measurements will be taken on pre-dose, 1, 3, and 6 hours post dose on Day 1 and on Day 15

  12. Objective Response Rate (ORR) - Phase 3 part

    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.

    Measured: When 247 Overall Survival (OS) events have occured (up to approximately 45 months)

  13. Progression-free survival (PFS) - Phase 3 part

    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.

    Measured: When 247 Overall Survival (OS) events have occured (up to approximately 45 months)

  14. Time to response (TTR) - Phase 3 part

    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.

    Measured: When 247 Overall Survival (OS) events have occured (up to approximately 45 months)

  15. Duration of Response (DoR) - Phase 3 part

    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.

    Measured: When 247 Overall Survival (OS) events have occured (up to approximately 45 months)

  16. Disease Control Rate (DCR) - Phase 3 part

    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.

    Measured: When 247 Overall Survival (OS) events have occured (up to approximately 45 months)

  17. Incidence of Adverse Events (AEs) - Phase 3 part

    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)

    Measured: When 247 Overall Survival (OS) events have occured (up to approximately 45 months)

  18. Health-related quality of life (QoL) - Phase 3 part

    QLQ-C30 and EORTC QLQ-STO22 questionnaire

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

  19. 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

    Phase 3 part: To assess on disease-related symptoms and health-related quality of life (QoL) of gastric cancer patients

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

  20. 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

    Phase 3 part: To assess on disease-related symptoms and health-related quality of life (QoL) of gastric cancer patients

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2017
  2. Study start31 Aug 2017
  3. Primary completion20 Dec 2018
  4. Study completion22 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03130790
Sponsor's protocol ID
ASLAN001-012
Status last verified
Feb 2022
First submitted
16 Apr 2017
Last updated
15 Feb 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Varlitinib and mFOLFOX6 in people with Gastric Cancer, run by ASLAN Pharmaceuticals at 16 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in South Korea, Taiwan, Lithuania, Thailand, Estonia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage change from baseline in tumor size at Week 12 - Phase 2 part (time frame: At baseline and every 6 weeks for 24 weeks, after which reduced to once every 12 weeks until progression (up to approximately 3 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2022.

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