Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Channel Blockers

Analgesics

Anticonvulsants

Central Nervous System Depressants

Reproductive Control Agents

Gemcitabine

Magnesium Sulfate

Cisplatin

Antimetabolites

Varlitinib (starting dose at 200 mg BID) Cisplatin Gemcitabine

Per oral (PO) Varlitinib BID (starting dose at 200 mg BID)

Varlitinib

On D1 and D8, every 3 weeks. Cisplatin (25 mg per square meter of body surface area) in 1 litre of 0.9% saline with 20 mmol of potassium chloride and 8 mmol of magnesium sulfate intravenous (IV) infusion for 2 hours, followed by 500 mL of 0.9% saline over 30 minutes before the administration of Gemcitabine

On D1 and D8, every 3 weeks. Gemcitabine (1000 mg per square meter of body surface area) as a 30-minute infusion.

ASLAN Pharmaceuticals ASLAN Pharmaceuticals

The study intends to evaluate the following objectives in patients with advanced or metastatic biliary tract cancer who have not received systemic therapy for advanced/metastatic disease.

Primary Objectives:

Phase 1B

* To determine the maximum tolerated dose (MTD), as determined by dose-limiting toxicities (DLTs), and to characterise the safety profile of Varlitinib in combination with Gemcitabine and Cisplatin.

Phase 2A

* To further evaluate the safety and tolerability of Varlitinib in combination with Gemcitabine and Cisplatin at the recommended phase 2 dose (RP2D).
* To provide a preliminary assessment of the clinical activity of Varlitinib in combination with Gemcitabine and Cisplatin at the RP2D as measured by Objective Response Rate (ORR) and progression-free survival (PFS) (based on RECIST v1.1)

Phase 2B

* To compare the efficacy of Varlitinib in combination with Gemcitabine and Cisplatin to placebo in combination with Gemcitabine and Cisplatin as measured by progression-free survival (based on RECIST v1.1).

In phase 1B part, patients will receive Varlitinib plus Gemcitabine and Cisplatin, and follow a modified 3+3+3 study dose escalation scheme starting from Varlitinib 200 mg BID. The primary objective of the phase 1B part is to determine the MTD of Varlitinib when given in combination with Gemcitabine and Cisplatin, and to characterise the safety profile of the study treatment regimen.

Based on the determined MTD and clinical information obtained from phase 1B part of the study, the DSMB will review the safety data and other clinical data, together with the sponsor, determine the MTD as well as the recommended phase 2 dose (RP2D). The sponsor will make a decision when to proceed with the phase 2A part of the study.

The phase 2A part of the study is designed as a single arm expansion, enrolling a further 20 patients at the RP2D. The purpose of the phase 2A expansion study is to confirm the safety and tolerability of the RP2D in a larger number of patients, and to provide preliminary estimates of the clinical activity of Varlitinib in combination with Gemcitabine and Cisplatin, prior to embarking on the larger, randomised phase 2B part of the trial.

The phase 2B part will be a two-arm, double-blinded, placebo controlled study. Patients will be randomised into 2 arms to receive Varlitinib plus Gemcitabine and Cisplatin, or placebo plus Gemcitabine and Cisplatin. The primary endpoint of the phase 2B part is progression-free survival (PFS). The randomisation will be stratified by primary tumour location (gall bladder or non-gall bladder).

Patient screening activities including informed consent and study eligibility verification will be performed within 21 days prior to first dose of the study medication. Radiological imaging to assess the disease status will be performed at baseline and every 6 weeks from Cycle 1 Day 1. Blood samples will be taken during the screening phase, treatment period until end of treatment. Patients will be required to complete safety follow-up within 28 days after the last administration of study medication.

Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic BTC

A Multicentre, Phase 1B/2 Study of Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic Biliary Tract Cancer.

To determine the maximum tolerated dose (MTD), as determined by dose-limiting toxicities (DLTs), and to characterise the safety and tolerability profile of Varlitinib as determined by the adverse events in combination with Gemcitabine and Cisplatin.

Determined by safety parameters (including vital signs, ECG parameters, clinical laboratory tests)

Other measures of tolerability such as dose interruptions, treatment exposure and dose intensity.

ORR is defined as the number (%) of patients with at least one visit response of CR or PR. Data obtained up until the earlier of progression or the last evaluable assessment prior to starting subsequent therapy, will be included in the assessment of ORR.

PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined in accordance with the RECIST v1.1 criteria and will be derived programmatically.

PFS is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined in accordance with the RECIST v1.1 criteria and will be derived programmatically based on data from the Independent Central Review (ICR) of radiological data.

ORR is defined as the number (%) of patients with at least one visit response of CR or PR. Data obtained up until progression or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR.

DCR is defined as the number (%) of patients with at least one visit response of CR or PR, or with stable disease for a minimum of twelve weeks (- 5 days) from randomisation (Phase 2B) or starting treatment (Phase 1B and Phase 2A). For Phase 2B, data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of DCR.

DoR is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.

OS is defined as time from the start of treatment (Phase 2A) or randomisation (Phase 2B) until death by any cause.

Changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests) as categorized in accordance to CTCAE v4.03

Area under the plasma concentration-time curve from 0 to 6 hours (AUC0-6), and area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12).

Accumulation ratio of AUC0-6 (Day 22) compared to AUC0-6 (Day 1) (RacAUC0-6), accumulation ratio of AUC0-12 (Day 22) compared to AUC0-12 (Day 1) (RacAUC0-12)

Accumulation ratio of Cmax (Day 22) compared to Cmax (Day 1) (RacCmax).

Accumulation ratio of Cmax (Day 22) compared to Cmax (Day 1) (RacCmax)

Area under the plasma concentration-time curve from 0 to 6 hours (AUC0-6), and area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12)

Volume of distribution at the terminal phase (Vz) and volume of distribution at the steady-state (Vss)

Area under the plasma concentration-time curve from 0 to t (AUC0-t), and area under the plasma concentration-time curve from 0 to infinite (AUC0-inf)

Accumulation ratio of AUC0-inf (Day 22) compared to AUC0-inf (Day 1) (RacAUC0-inf)

ASLAN Pharmaceuticals

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

varlitinib tablets with:

1. starting dose: 300mg BID
2. target dose: 400mg BID
3. dose modification by investigator allowed between 200mg BID to 500mg BID

Please contact us for more information

This is a single arm, multicentre, Phase 2 study to assess efficacy and safety of ASLAN001 in patients with advanced or metastatic cholangiocarcinoma who progressed on at least 1 line of systemic therapy.

25 evaluable patients will be enrolled in the study. After evaluation of initial response in the first 10 evaluable patients, Sponsor will make a decision on recruitment of an additional 15 evaluable patients. If no response is observed, the study will stop.

The primary objective is to assess efficacy of varlitinib (also known as ASLAN001) as measured by ORR (based on RECIST v1.1). The secondary objectives are to (1) evaluate the efficacy of varlitinib, as measured by DoR, PFS, OS and DCR, (2) assess ORR, DoR, PFS, DCR and OS by tumor EGFR/HER2 status, (3) assess safety and tolerability of ASLAN001 monotherapy. Exploratory objectives are to explore possible relationships between response to ASLAN001 and the protein expression levels and gene mutational status of the proteins and genes via IHC and PCR/Sequencing.

Cholangiocarcinoma (CCA) is a malignancy arising from the biliary epithelium characterized by poor prognosis and poor response to current treatments. Emerging at any portion of the biliary tree, it includes a group of tumours with epidemiologic, morphologic, biologic, and clinical heterogeneity. Despite recent medical advances, the long-term outcomes and recurrence rates for CCA are poor. The 5-year survival rate following surgical resection is 11-40%. Tumour recurrence rates are as high as 50-65%, with a median time to recurrence between 12-43 months.

In the United States, the incidence and mortality of CCA have increased over the last 30 years without clear underlying etiological reasons. The only curative therapy is surgical; however this is not an option for many patients given the stage of the disease at presentation and metastasis. While improvements in diagnostic modalities and neoadjuvant chemotherapy have allowed for detection at earlier stages and greater survival rates, the prognosis is still unfavorable. Therapies that can decrease tumour growth, improve resection outcomes, increase survival rates, and decrease recurrence would make a great impact on the quality of life of CCA patients and are urgently needed.

Currently, the Food and Drug Administration (FDA)-approved agents used in unresectable CCA include gemcitabine, capecitabine, cisplatin, oxaliplatin, fluoropyrimidines (including 5-fluorouracil), or a combination of these. However, none are FDA-approved primarily for use in CCA specifically. Gemcitabine and cisplatin combination therapy, along with fluoropyrimidine-based or other gemcitabine-based regimens are part of the guidelines for unresectable cancer per the National Comprehensive Cancer Network. To date, the most effective chemotherapy regimen is administration of gemcitabine with cisplatin or oxaliplatin, which have now become the standard of care for systemic therapy. Even this most efficacious treatment has been found to only modestly increase overall survival (11.7 months vs 8.3 months for patients receiving gemcitabine alone) and progression-free survival (8.4 vs 6.5 months). Standard treatment as second-line chemotherapy for CCA is unclear as there is no significant evidence for specific therapy which indicates that further chemotherapy beyond progression on first-line chemotherapy improves survival.

CCA involves mutations in members of the ErbB family, including EGFR and HER2 mutations. EGFR is overexpressed in both intrahepatic and extrahepatic CCA (30.8% and 20.9%, respectively) and is an independent prognostic factor in intrahepatic cases, per Yang et al 2014. While this study found overexpression of HER2 exclusively in extrahepatic samples (and only in 4.5% of these), previous studies have implicated this protein in both extra- and intrahepatic tumours. Settakorn et al (2005) showed HER2 expression is correlated with high histological grade in intrahepatic CCA. Kim et al. (2007) found HER2 (gene and protein levels) are overexpressed in approximately 30% of extrahepatic CCA patients and is a prognostic factor for survival in those with lymph node metastasis.

EGFR, HER2, and HER4 are single-pass transmembrane glycoprotein receptors, members of the type I receptor tyrosine kinase family. Upon ligand binding, their activation induces the homo- or heterodimerization and subsequent phosphorylation of intracellular tyrosines, which lead to both cell proliferation and survival and therefore cancer development and progression. EGFR and HER2 inhibitors have both demonstrated clinical efficacy in cancer treatment. The simultaneous inhibition of both represents a new therapeutic approach for broadly targeting different tumour types that may be more effective than selective inhibition of each receptor.

Varlitinib, also known as ASLAN001 is a potent, orally active inhibitor of the receptor tyrosine kinases epidermal growth factor (EGFR) and human epidermal growth factor receptors 2 and 4 (HER2, HER4). In cell-based assays, varlitinib has been shown to potently inhibit the phosphorylation of EGFR, HER2, and HER4 in a dose-dependent manner. In cell lines overexpressing HER2, varlitinib also inhibited the phosphorylation of the HER2 downstream effector AKT.

ASLAN hypothesises that varlitinib will inhibit EGFR, HER2, HER4 as their mutations results in CCA, thus in turn inhibiting the growth of cancerous cells and development/progression. ASLAN believes that varlitinib is a compound that may be beneficial to patients with cancer by simultaneous inhibition of these receptors.

ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy

A Phase 2A, Single Arm, Multicentre, Study of ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy

Possible relationship of protein expression level and gene mutational status determined from archival material or biopsy tissue samples with response to ASLAN001, using IHC, PCR/Sequencing and if additional material is available, IHC staining methods.

Defined as the proportion of patients with a response of PR or CR, as defined by RECIST v1.1 criteria. Data obtained up until disease progression, or last evaluable assessment in the absence of disease progression, will be included in the assessment of ORR.

PFS is defined as the time from start of treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) regardless of whether the patient withdraws from study therapy or receives another antitumour therapy prior to disease progression.

Defined as proportion of patients with a best response of stable disease or better as defined by RECIST v1.1 criteria. Note, a minimum interval of 6 weeks (±5 days) from first dose is required for a patient to be attributed a best response of stable disease. Data obtained up until disease progression, or last evaluable assessment in the absence of disease progression, will be included in the assessment of DCR.

Defined as the time from the date of first documented response until the date of documented disease progression or death in the absence of disease progression, the end of response should coincide with the date of disease progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR.

If a patient does not progress following a response, then their DoR will use the PFS censoring time.

Defined as the time from the date of start of treatment until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

Patient safety will be evaluated based on physical examination, vital signs (blood pressure \[systolic and diastolic\], resting pulse, respiratory rate, weight and body temperature), ECG parameters, clinical laboratory tests (hematology, clinical chemistry, coagulation and urinalysis) and AEs.

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

Micronutrients

Leucovorin

Fluorouracil

Oxaliplatin

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

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.

mFOLFOX6

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

Placebo

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.

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.

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

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

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

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.

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.

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.

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.

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.

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.

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.

Phase 2 part: Pharmacokinetic of Varlitinib

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.

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.

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.

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.

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.

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)

QLQ-C30 and EORTC QLQ-STO22 questionnaire

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

Gallbladder Neoplasms

Bile Duct Neoplasms

Capecitabine

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

1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

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

Placebo (for Varlitinib)

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

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.

Treatment: protocol designed to evaluate one or more interventions for treating a disease, syndrome or condition

Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer

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

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).

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.

The ORR rate 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. In all study parts, the primary assessment of ORR was based on the Full Analysis Set (FAS).

Part 1: Overall survival (OS) was defined as the time from the date of randomization until death due to any cause. Any subject not known to have died at the time of the data cut-off was censored based on the last recorded date on which the subject was known to be alive.

Part 1: Duration of response (DoR) was defined as the time from the date of first documented response until the date of documented PD or death in the absence of disease progression. The end of the response should have coincided with the date of disease progression or death from any cause used for the PFS endpoint.

For Part 1, DoR was calculated based on data from the ICR of radiological data.

Part 1: DCR rate was defined as the number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization. Data obtained up until progression, or until last evaluable assessment in the absence of progression, were included in the assessment of DCR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. For all study parts, the primary assessment of DCR was based on the FAS.

For Part 1, DCR was calculated based on data from the ICR

Part 1: The percentage change from baseline in tumor size at Week 12 (%ΔTSWk12) was a secondary endpoint for Part 1 and was used to present waterfall plots of the target lesion data in the Evaluable for Response (EFR) Population

Clinical laboratory tests (hematology, clinical chemistry, urinalysis) - Number of Participants with Clinically Significant Laboratory Tests.

Number of participants with clinically significant change in vital signs (blood pressure \[diastolic and systolic\], heart rate, respiratory rate, body temperature) and physical examination.

Number of participants with ECG parameters of interest: Max. on-treatment QTcF Value: \>450 to 480 msec, max. on-treatment QTcF Value: \>480 to 500 msec, max. on-treatment QTcF Value: \>500 msec, max. on-treatment QTcB Value: \>450 to 480 msec, max. on-treatment QTcB Value: \>480 to 500 msec, max. on-treatment QTcB Value: \>500 msec, max. QTcF CFB Value: \>30 to 60 msec, max. QTcF CFB Value: \>60 msec, max. QTcB CFB Value: \>30 to 60 msec, max. QTcB CFB Value: \>60 msec.

Number of participants with ECG parameters of interest: Max. on-treatment QTcF Value: \<=450 msec, max. on-treatment QTcF Value: \>450 to 480 msec, max. on-treatment QTcF Value: \>480 to 500 msec, max. on-treatment QTcF Value: \>500 msec, max. on-treatment QTcB Value: \<=450 msec, max. on-treatment QTcB Value: \>450 to 480 msec, max. on-treatment QTcB Value: \>480 to 500 msec, max. on-treatment QTcB Value: \>500 msec, max. QTcF CFB Value: \<=30 msec, max. QTcF CFB Value: \>30 to 60 msec, max. QTcF CFB Value: \>60 msec, max. QTcB CFB Value: \<=30 msec, max. QTcB CFB Value: \>30 to 60 msec, max. QTcB CFB Value: \>60 msec.

Eastern Cooperative Oncology Group (ECOG) Performance was clinically graded based on the following:

Grade 0 = Normal activity. Fully active, able to carry on all pre-disease performance without restriction.

Grade 1 = Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).

Grade 2 = In bed \< 50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.

Grade 3 = In bed \> 50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.

Grade 4 = 100% bedridden. Completely disabled. Cannot carry on any self- care. Totally confined to bed or chair.

Grade 5 = Death

bioRASI, LLC

CMIC Co, Ltd. Japan

Syneos Health

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

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Varlitinib and Capecitabine - Safety Lead-In

Varlitinib and Capecitabine - Part 1

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo and Capecitabine - Part 1

Total

Safety Lead-In

Part 1

The study consists of Safety Lead-In (24 patients in Varlitinib + Capecitabine group) and Part 1 (64 patients in Varlitinib + Capecitabine group, 63 patients in Placebo + Capecitabine group)

Age, Continuous

Sex: Female, Male

Overall Study

Ethnicity (NIH/OMB)

Race (NIH/OMB)

South Korea

Hungary

United States

Japan

Taiwan

Poland

Australia

Spain

Singapore

Region of Enrollment

BMI - Safety Lead-in

BMI - Part 1

Study Director

Varlitinib and Capecitabine

Placebo and Capecitabine

Objective Response Rate (ORR) - Part 1

Progression-free Survival (PFS) - Part 1

This part of the study was a single arm, open-label design to assess the safety of varlitinib (300 mg administered BID every day) plus capecitabine (1000 mg/m2 administered BID every day for 14 days, followed by a 7-day rest period) in a small set of subjects (12 to 20 subjects) with 12 subjects completing the PK and ECG evaluations. Treatment was continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or death.

Varlitinib + Capecitabine

Object Response Rates (ORR) - Safety Lead-In

Overall Survival (OS) - Part 1

Overall Survival (OS) - Safety Lead-In

Kaplan Meier median is presented for DoR. At the time of reporting, there were 3 censored observations in the V+C arm, none in the P+C arm. The observed number of responders in the trial was much lower than anticipated; 9 responders in total, 6 for varlitinib and 3 for placebo. Based on results of the primary endpoints, the follow-up analysis to provide more long-term efficacy data planned for when 70% of patients had experienced an OS event was not undertaken based on pre-specified criteria.

Duration of Response (DoR) - Part 1

Disease Control Rate DCR - Part 1

Tumor Size - Part 1

No subjects reported with any CS values across majority of the hematologic, clinical chemistry, urinalysis parameters during the Safety Lead-In of the study

Number of Participants With Clinically Significant Laboratory Tests- Safety Lead-in

No subjects reported with any CS values across majority of the hematologic, clinical chemistry and urinalysis parameters at the end of treatment.

Number of Participants With Clinically Significant Laboratory Tests - Part 1

Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Safety Lead-In

Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Part 1

Maximum on-treatment QTcF Value: >450 to 480 msec

Maximum on-treatment QTcF Value: >480 to 500 msec

Maximum on-treatment QTcF Value: >500 msec

Maximum on-treatment QTcB Value: >450 to 480 msec

Maximum on-treatment QTcB Value: >480 to 500 msec

Maximum on-treatment QTcB Value: >500 msec

Maximum QTcF CFB Value: >30 to 60 msec

Maximum QTcF CFB Value: >60 msec

Maximum QTcB CFB Value: >30 to 60 msec

Maximum QTcB CFB Value: >60 msec

Number of Participants With ECG Parameters of Interest - Safety Lead-In

Maximum on-treatment QTcF Value: <=450 msec

Maximum on-treatment QTcB Value: <=450 msec

Maximum QTcF CFB Value: <=30 msec

Maximum QTcB CFB Value: <=30 msec

Number of Participants With ECG Parameters of Interest - Part 1

For the Varlitinib 300 mg BID + Capecitabine treatment group, ECOG Performance Status scores ranged from 0 to 3 at EOT.

For the Placebo + Capecitabine treatment group, ECOG Performance Status scores ranged from 0 to 3 at EOT.

ECOG Performance Status - Part 1

* PO varlitinib 300 mg BID
* PO capecitabine 1000 mg/m2 BID

from Day 1 to Day 14 followed by 7-day of rest period, every 21 days.

The purpose of the study is to assess the efficacy of varlitinib in combination with capecitabine as measured by objective response rate (ORR) assessed by independent central review (ICR), based on RECIST v1.1 criteria.

Also to explore the role of biomarkers as predictors of response and clinical benefit with varlitinib

Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.

Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer

A Phase 2, Single Arm Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as First-line Systemic Therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic BTC	NCT02992340	Biliary Tract C...	Varlitinib Cisplatin Gemcitabine	-	ASLAN Pharmaceuticals
ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy	NCT02609958	Cholangiocarcin...	Varlitinib	-	ASLAN Pharmaceuticals
Varlitinib in Combination With mFOLFOX6 for Advanced or Metastatic Gastric Cancer (First Line)	NCT03130790	Gastric Cancer	Varlitinib mFOLFOX6 Placebo mFOLFOX6	21 Years -	ASLAN Pharmaceuticals
Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic BTC	NCT02992340	Biliary Tract C...	Varlitinib Cisplatin Gemcitabine	-	ASLAN Pharmaceuticals
Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer	NCT03093870	Biliary Tract C...	Varlitinib Capecitabine Placebo (for Va...	-	ASLAN Pharmaceuticals
Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer	NCT03093870	Biliary Tract C...	Varlitinib Capecitabine Placebo (for Va...	-	ASLAN Pharmaceuticals
Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer	NCT03129074	Advanced or Met...	Varlitinib Capecitabine	18 Years -	ASLAN Pharmaceuticals
Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-FU or Cisplatin and Capecitabine	NCT02648425	Solid Tumor	ASLAN001 cisplatin + cap... cisplatin + 5-f...	20 Years -	ASLAN Pharmaceuticals
ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy	NCT02609958	Cholangiocarcin...	Varlitinib	-	ASLAN Pharmaceuticals
Varlitinib in Combination With mFOLFOX6 for Advanced or Metastatic Gastric Cancer (First Line)	NCT03130790	Gastric Cancer	Varlitinib mFOLFOX6 Placebo mFOLFOX6	21 Years -	ASLAN Pharmaceuticals
Varlitinib Plus Capecitabine in Chinese Patients With Advanced or Metastatic Biliary Tract Cancer	NCT03231176	Biliary Tract C...	Varlitinib Capecitabine	18 Years - 99 Years	ASLAN Pharmaceuticals
A Study of Varlitinib in Japanese Subjects With Advanced or Metastatic Solid Tumours	NCT03082053	Advanced or Met... Advanced or Met...	varlitinib capecitabine	20 Years -	ASLAN Pharmaceuticals

Spots Global Cancer Trial Database for varlitinib

Every month we try and update this database with for varlitinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for varlitinib

Every month we try and update this database with for varlitinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for varlitinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.