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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 January 2021
• Main ID: NCT02992340
• Date of registration: 08/12/2016
• Prospective Registration: Yes
• Primary sponsor: Aslan Pharmaceuticals
• Public title: Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic BTC
• Scientific title: A Multicentre, Phase 1B/2 Study of Varlitinib in Combination With Gemcitabine and Cisplatin for Treatment naïve Advanced or Metastatic Biliary Tract Cancer.
• Date of first enrolment: December 13, 2016
• Target sample size: 204
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02992340
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Korea, Republic of, Singapore, Taiwan

Contacts

• Name: ASLAN Pharmaceuticals ASLAN Pharmaceuticals
• Affiliation: [e-mail]

Key inclusion & exclusion criteria

Inclusion Criteria:

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

2. 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.

3. 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.

4. 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.

5. 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).

6. Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. 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

Exclusion Criteria:

1. Patients with radiation or local treatment 6 weeks prior to screening for the target
lesion(s).

2. Patients with major surgical procedures within 21 days prior to screening.

3. Patients with known brain metastases.

4. 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.

5. Pre-existing peripheral sensory neuropathy = grade 2 according to CTCAE (v.4.03).

6. 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.

7. 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).

8. 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.

9. 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.

10. Patients with known history of drug addiction within last 1 year.

11. Patients who may need continuous treatment with proton pump inhibitors or strong
CYP3A4 inhibitors during the study period.

12. Female patients who are pregnant or breast-feeding.

13. 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.

14. Patients who have received immunotherapy for cancer, including but not limited to
immune checkpoint inhibitors, monoclonal antibody, cancer vaccine, and cell therapy.

15. Patient with unresolved or unstable serious toxicity (= CTCAE 4.03 Grade 2) from prior
administration of another investigational drug and/or prior cancer treatment.

16. 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.



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Biliary Tract Cancer

Intervention(s)

Drug: Cisplatin

Drug: Gemcitabine

Drug: Varlitinib

Primary Outcome(s)

Phase 1B: Maximum tolerated dose (MTD) of Varlitinib [Time Frame: DLT period is 3 weeks]

Phase 2A: Objective Response Rate (ORR) [Time Frame: Through study duration, estimated 3 years]

Phase 2A: Safety and tolerability [Time Frame: Through study duration, estimated 3 years]

Phase 2B: Progression Free Survival (PFS) [Time Frame: Through study duration, estimated 3 years]

Phase 1B: Safety and toxicity [Time Frame: Through study duration, estimated 3 years]

Phase 2A: Progression Free Survival (PFS) [Time Frame: Through study duration, estimated 3 years]

Secondary Outcome(s)

Overall Survival (OS) (Phase 2A and Phase 2B only) [Time Frame: Through study duration, estimated 3 years]

Pharmacokinetics of Gemcitabine, dFdU (gemcitabine metabolite) and Cisplatin (Phase 2B) [Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1]

Duration of response (DoR) (Phase 1B, Phase 2A and Phase 2B) [Time Frame: Through study duration, estimated 3 years]

Incidence of AEs (Phase 2B) [Time Frame: Through study duration, estimated 3 years]

Objective Response Rate (Phase 2B) [Time Frame: Through study duration, estimated 3 years]

Pharmacokinetics of Varlitinib (Phase 2B) [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 2B) [Time Frame: Cycle 2 Day 1]

Disease control rate (DCR) (Phase 1B, Phase 2A and Phase 2B) [Time Frame: Through study duration, estimated 3 years]

Objective Response Rate (ORR)(Phase 1B) [Time Frame: Through study duration, estimated 3 years]

Secondary ID(s)

ASLAN001-007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors