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

NCT02992340 | Terminated Phase 1 DMC

• 1 other identifier: ASLAN001-007
• Study Type: interventional
• Target: 204
• Locations: 3 countries
• Sites: 3

Brief 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. 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).

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (8)

• 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.

  DLT period is 3 weeks

• Phase 1B: Safety and toxicity

  Determined by the adverse events.

  Through study duration, estimated 3 years

• Phase 2A: Safety and tolerability

  Determined by adverse events

  Through study duration, estimated 3 years

• Phase 2A: Safety and tolerability

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

  Through study duration, estimated 3 years

• Phase 2A: Safety and tolerability

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

  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.

  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.

  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.

  Through study duration, estimated 3 years

Secondary Outcomes (29)

• Objective Response Rate (ORR)(Phase 1B)

  Through study duration, estimated 3 years

• Objective Response Rate (Phase 2B)

  Through study duration, estimated 3 years

• Disease control rate (DCR) (Phase 1B, Phase 2A and Phase 2B)

  Through study duration, estimated 3 years

• Duration of response (DoR) (Phase 1B, Phase 2A and Phase 2B)

  Through study duration, estimated 3 years

• Overall Survival (OS) (Phase 2A and Phase 2B only)

  Through study duration, estimated 3 years

Study Arms (1)

Phase 1B

EXPERIMENTAL

Varlitinib (starting dose at 200 mg BID) Cisplatin Gemcitabine

Drug: Varlitinib; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Varlitinib DRUG

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

Also known as: ASLAN001

Phase 1B

Cisplatin DRUG

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

Phase 1B

Gemcitabine DRUG

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

Phase 1B

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ASLAN Pharmaceuticals: lead

Study Sites (3)

Unknown Facility

Singapore, Singapore

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

Taipei, Taiwan

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• ASLAN Pharmaceuticals ASLAN Pharmaceuticals

  contact@aslanpharma.com

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2016
• First Posted: December 14, 2016
• Study Start: December 13, 2016
• Primary Completion: June 16, 2020
• Study Completion: November 24, 2020
• Last Updated: January 14, 2021

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1); TW (1); SG (1)