Biliary Tract CancerPhase 1/2NCT02992340
Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic BTC
A Phase 1/2 study testing Varlitinib, Cisplatin and Gemcitabine in people with Biliary Tract Cancer, run by ASLAN Pharmaceuticals at 3 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Biliary Tract Cancer
- What is being tested?
- Varlitinib, Cisplatin and Gemcitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 204 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 13 Dec 2016to 24 Nov 2020
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient of respective country's legal age or older at the time of written informed consent.
- Patient must be able to understand and willing to provide informed consent for participation in the study and donation of tumour tissue (archival or fresh) for evaluation of relevant exploratory endpoints.
- Patient must have histologically or cytologically confirmed advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or carcinoma of the Ampulla of Vater, with no prior systemic therapy for advanced/metastatic disease. This includes clinical diagnosis of biliary tract cancer with histological confirmation of adenocarcinoma.
- For phase 1B and 2A only: Presence of radiologically measured disease with at least one, not previously irradiated, measurable lesion according to RECIST v.1.1.
- No evidence of clinically significant biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below or equal to 1.5 x upper level of normal (ULN).
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Patient with adequate organ and haematological function prior to first dose of study medication:
- Haematological function, as follows: i. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ii. Platelet count ≥ 100 x 109/L iii. Haemoglobin level ≥ 10 g/dl 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 ≤ 5 x ULN
Who cannot join
- Patients with radiation or local treatment 6 weeks prior to screening for the target lesion(s).
- Patients with major surgical procedures within 21 days prior to screening.
- Patients with known brain metastases.
- Patients with malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications which in the opinion of the Investigator could jeopardize the validity of the study results. Any extent of stomach resection will be excluded.
- Pre-existing peripheral sensory neuropathy ≥ grade 2 according to CTCAE (v.4.03).
- Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, diabetes, hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
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- Patients with any history of other malignancy unless in remission for more than 1 year prior to screening (Non-melanoma skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative intent is not exclusionary).
- Patients with a known history of HIV, decompensated cirrhosis, HCV infection, and for phase 1B: HBV infection with detectable HBV deoxyribonucleic acid (DNA) or abnormal transaminase; for phase 2A \& 2B: HBV infection with HBV DNA exceeding 2000 IU/mL.
- Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition, which, in the opinion of the investigator, could jeopardise the safety of the patient or the validity of the study results.
- Patients with known history of drug addiction within last 1 year.
- Patients who may need continuous treatment with proton pump inhibitors or strong CYP3A4 inhibitors during the study period.
- Female patients who are pregnant or breast-feeding.
- Patients who have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication.
- Patients who have received immunotherapy for cancer, including but not limited to immune checkpoint inhibitors, monoclonal antibody, cancer vaccine, and cell therapy.
- Patient with unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment.
- Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or have a history of interstitial lung disease or current interstitial lung disease.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: A Multicentre, Phase 1B/2 Study of Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic Biliary Tract Cancer.
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:
Read more
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).
Read the detailed description
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.
- Conditions
- Biliary Tract Cancer
- Being tested
- Varlitinib, Cisplatin, Gemcitabine
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VarlitinibDrug
Also called ASLAN001
Per oral (PO) Varlitinib BID (starting dose at 200 mg BID)
CisplatinDrug
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
GemcitabineDrug
On D1 and D8, every 3 weeks. Gemcitabine (1000 mg per square meter of body surface area) as a 30-minute infusion.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1B | Experimental | Varlitinib (starting dose at 200 mg BID) Cisplatin Gemcitabine Receives: Drug: Varlitinib; Drug: Cisplatin; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1B: Maximum tolerated dose (MTD) of Varlitinib
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.
Measured: DLT period is 3 weeks
Phase 1B: Safety and toxicity
Determined by the adverse events.
Measured: Through study duration, estimated 3 years
Phase 2A: Safety and tolerability
Determined by adverse events
Measured: Through study duration, estimated 3 years
Phase 2A: Safety and tolerability
Determined by safety parameters (including vital signs, ECG parameters, clinical laboratory tests)
Measured: Through study duration, estimated 3 years
Phase 2A: Safety and tolerability
Other measures of tolerability such as dose interruptions, treatment exposure and dose intensity.
Measured: Through study duration, estimated 3 years
Phase 2A: Objective Response Rate (ORR)
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.
Measured: Through study duration, estimated 3 years
Phase 2A: Progression Free Survival (PFS)
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.
Measured: Through study duration, estimated 3 years
Phase 2B: Progression Free Survival (PFS)
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.
Measured: Through study duration, estimated 3 years
Secondary outcomes (29)
Objective Response Rate (ORR)(Phase 1B)
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.
Measured: Through study duration, estimated 3 years
Objective Response Rate (Phase 2B)
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.
Measured: Through study duration, estimated 3 years
Disease control rate (DCR) (Phase 1B, Phase 2A and Phase 2B)
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.
Measured: Through study duration, estimated 3 years
Duration of response (DoR) (Phase 1B, Phase 2A and Phase 2B)
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.
Measured: Through study duration, estimated 3 years
Overall Survival (OS) (Phase 2A and Phase 2B only)
OS is defined as time from the start of treatment (Phase 2A) or randomisation (Phase 2B) until death by any cause.
Measured: Through study duration, estimated 3 years
Incidence of AEs (Phase 2B)
Changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests) as categorized in accordance to CTCAE v4.03
Measured: Through study duration, estimated 3 years
Pharmacokinetics of Varlitinib (Phase 1B)
Maximum plasma concentration (Cmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time to Cmax (tmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
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).
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Pre-dose concentration (Ctrough)
Measured: Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
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)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Accumulation ratio of Cmax (Day 22) compared to Cmax (Day 1) (RacCmax).
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Accumulation ratio of Cmax (Day 22) compared to Cmax (Day 1) (RacCmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Maximum plasma concentration (Cmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time to Cmax (tmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
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)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Pre-dose concentration (Ctrough)
Measured: Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
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)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Accumulation ratio of Cmax (Day 22) compared to Cmax (Day 1) (RacCmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Maximum plasma concentration (Cmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time to Cmax (tmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Last measurable concentration (Clast)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Terminal half-life (t1/2)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Mean residence time (MRT)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Volume of distribution at the terminal phase (Vz) and volume of distribution at the steady-state (Vss)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Plasma clearance (Cl)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
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)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Accumulation ratio of AUC0-inf (Day 22) compared to AUC0-inf (Day 1) (RacAUC0-inf)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Accumulation ratio of Cmax (Day 22) compared to Cmax (Day 1) (RacCmax)
Measured: Cycle 1 Day 1 and Cycle 2 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study start13 Dec 2016
- Primary completion16 Jun 2020
- Study completion24 Nov 2020
Why it stopped: Sponsor decided to terminate the study and not proceed to Phase 2.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Biliary Tract CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 204 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ASLAN Pharmaceuticals
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- ASLAN Pharmaceuticals ASLAN Pharmaceuticals, Study director, contact@aslanpharma.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02992340
- Sponsor's protocol ID
- ASLAN001-007
- Status last verified
- Jan 2020
- First submitted
- 8 Dec 2016
- Last updated
- 14 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Phase 1B/2 Study of Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic Biliary Tract Cancer.
- ClinicalTrials.gov ID
- NCT02992340
- Acronym / sponsor ID
- ASLAN001-007
- Conditions
- Biliary Tract Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decided to terminate the study and not proceed to Phase 2.
- Enrolment
- 204 participants (estimated)
- Lead sponsor
- ASLAN PharmaceuticalsUniversity, hospital or other
- Study start
- 13 Dec 2016 (actual)
- Primary completion
- 16 Jun 2020 (actual)
- Study completion
- 24 Nov 2020 (actual)
- First posted
- 14 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1B | Experimental | Drug: Varlitinib, Drug: Cisplatin, Drug: GemcitabineVarlitinib (starting dose at 200 mg BID) Cisplatin Gemcitabine |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patient of respective country's legal age or older at the time of written informed consent.
- Patient must be able to understand and willing to provide informed consent for participation in the study and donation of tumour tissue (archival or fresh) for evaluation of relevant exploratory endpoints.
- Patient must have histologically or cytologically confirmed advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or carcinoma of the Ampulla of Vater, with no prior systemic therapy for advanced/metastatic disease. This includes clinical diagnosis of biliary tract cancer with histological confirmation of adenocarcinoma.
- For phase 1B and 2A only: Presence of radiologically measured disease with at least one, not previously irradiated, measurable lesion according to RECIST v.1.1.
- No evidence of clinically significant biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below or equal to 1.5 x upper level of normal (ULN).
Key exclusion criteria (16 listed)
- Patients with radiation or local treatment 6 weeks prior to screening for the target lesion(s).
- Patients with major surgical procedures within 21 days prior to screening.
- Patients with known brain metastases.
- Patients with malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications which in the opinion of the Investigator could jeopardize the validity of the study results. Any extent of stomach resection will be excluded.
- Pre-existing peripheral sensory neuropathy ≥ grade 2 according to CTCAE (v.4.03).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VarlitinibAlso: ASLAN001Per oral (PO) Varlitinib BID (starting dose at 200 mg BID) | Drug | Phase 1B |
| CisplatinOn 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 | Drug | Phase 1B |
| GemcitabineOn D1 and D8, every 3 weeks. Gemcitabine (1000 mg per square meter of body surface area) as a 30-minute infusion. | Drug | Phase 1B |
Primary outcome
Phase 1B: Maximum tolerated dose (MTD) of Varlitinib
Time frame: DLT period is 3 weeks
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.
Phase 1B: Safety and toxicity
Time frame: Through study duration, estimated 3 years
Determined by the adverse events.
Phase 2A: Safety and tolerability
Time frame: Through study duration, estimated 3 years
Determined by adverse events
Phase 2A: Safety and tolerability
Time frame: Through study duration, estimated 3 years
Determined by safety parameters (including vital signs, ECG parameters, clinical laboratory tests)
Phase 2A: Safety and tolerability
Time frame: Through study duration, estimated 3 years
Other measures of tolerability such as dose interruptions, treatment exposure and dose intensity.
Phase 2A: Objective Response Rate (ORR)
Time frame: Through study duration, estimated 3 years
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.
Phase 2A: Progression Free Survival (PFS)
Time frame: Through study duration, estimated 3 years
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.
Phase 2B: Progression Free Survival (PFS)
Time frame: Through study duration, estimated 3 years
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.
29 secondary outcomes
Objective Response Rate (ORR)(Phase 1B)
Time frame: Through study duration, estimated 3 years
Objective Response Rate (Phase 2B)
Time frame: Through study duration, estimated 3 years
Disease control rate (DCR) (Phase 1B, Phase 2A and Phase 2B)
Time frame: Through study duration, estimated 3 years
Duration of response (DoR) (Phase 1B, Phase 2A and Phase 2B)
Time frame: Through study duration, estimated 3 years
Overall Survival (OS) (Phase 2A and Phase 2B only)
Time frame: Through study duration, estimated 3 years
Incidence of AEs (Phase 2B)
Time frame: Through study duration, estimated 3 years
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 1B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time frame: Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Varlitinib (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1
Results and safety
The study was stopped early (reason given: Sponsor decided to terminate the study and not proceed to Phase 2.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ASLAN Pharmaceuticals ASLAN Pharmaceuticals study director
contact@aslanpharma.com
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Varlitinib, Cisplatin and Gemcitabine in people with Biliary Tract Cancer, run by ASLAN Pharmaceuticals at 3 sites in 3 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 8 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: stopped early, as of the sponsor's last update on 14 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Singapore, South Korea, Taiwan. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Sponsor decided to terminate the study and not proceed to Phase 2.). Results are not available in the source record.
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?
Phase 1B: Maximum tolerated dose (MTD) of Varlitinib (time frame: DLT period is 3 weeks). The study lists 8 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 14 Jan 2021.