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

NCT03093870 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ASLAN001-009
• Study Type: interventional
• Target: 151
• Locations: 11 countries
• Sites: 21

Brief Summary

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

Conditions

Biliary Tract Cancer

Keywords

Neoplasms; Biliary Tract Neoplasms; Bile Duct Neoplasms; Gallbladder Neoplasms

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) - Part 1

  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).

  Data obtained up until progression, or until last evaluable assessment in the absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.

• Progression-free Survival (PFS) - Part 1

  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.

  Time from randomization until date of objective disease progression or death (by any cause in absence of disease progression) regardless of whether subject withdrew from randomized therapy or received another antitumor therapy prior to PD, up to 2 years.

Secondary Outcomes (13)

• Object Response Rates (ORR) - Safety Lead-In

  Data obtained up until progression, or until last evaluable assessment in absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.

• Overall Survival (OS) - Part 1

  Time from the date of randomization until death due to any cause, up to 2 years

• Overall Survival (OS) - Safety Lead-In

  Time from the date of randomization until death due to any cause, up to 2 years

• Duration of Response (DoR) - Part 1

  Time from the date of first documented response until the date of documented PD or death in the absence of disease progression, up to 2 years

• Disease Control Rate DCR - Part 1

  Number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization.

Study Arms (2)

Varlitinib and Capecitabine

EXPERIMENTAL

Drug: Varlitinib; Drug: Capecitabine

Placebo and Capecitabine

PLACEBO COMPARATOR

Drug: Capecitabine; Drug: Placebo (for Varlitinib)

Interventions

Varlitinib DRUG

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

Also known as: ASLAN001, ARRY-334543, QBT01

Varlitinib and Capecitabine

Capecitabine DRUG

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; Varlitinib and Capecitabine

Placebo (for Varlitinib) DRUG

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

Placebo and Capecitabine

Eligibility Criteria

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

You may qualify if:

• Subjects will be eligible for the study if they:
• Are of or older than the legal age in the respective countries at the time when written informed consent is obtained
• Have histologically or cytologically confirmed advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma (CCA), gallbladder cancer and carcinoma of Ampulla of Vater. This includes clinical diagnosis of biliary tract cancer with histological confirmation of adenocarcinoma.
• Have received and failed one and only one prior line of systemic treatment for advanced or metastatic disease with radiologic evidence of disease progression. This prior line of systemic treatment must also contain gemcitabine
• Have received at least 6 doses of gemcitabine containing treatment in first line (Adjuvant therapy is not regarded as 1st line therapy)
• Have radiographically measurable disease based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by Independent Central Review (ICR) (For Part 1)
• Have no evidence of 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 × upper level of normal (ULN)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Are able to understand and willing to sign the informed consent form
• Have adequate organ and hematological function:
• Hematological function, as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L
• Renal functions, as follows:
• Estimated glomerular filtration rate or creatinine clearance \> 50 mL/min/1.73m2

You may not qualify if:

• Subjects will be ineligible for the study if they:
• Are currently on or have received anti-cancer therapy within the past 3 weeks before receiving the first dose of study medication
• Are currently on or have received radiation or local treatment within the past 3 weeks for the target lesion(s) before receiving the first dose of study medication
• Have evidence of multiple (≥ 2) peritoneal metastases or ascites at baseline as assessed by ICR (For Part 1). (Ascites which can be attributed by non-malignant causes is not excluded. Minimal ascites, which does not require paracentesis is permitted.)
• Have had major surgical procedures within 14 days prior to first dose of study medication
• Have a known metastatic brain lesion(s), including asymptomatic and well controlled lesion(s)
• Have 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
• Have 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
• Are female patients who are pregnant or breast feeding
• Have been previously treated with varlitinib or have been previously treated with capecitabine as first line therapy for advanced or metastatic disease. For patients who have previously received capecitabine as a radiosensitizer or as part of their adjuvant therapy and their disease has relapsed for more than 6 months after their last dose of capecitabine adjuvant therapy, their capecitabine therapy will not be considered as a line of systemic chemotherapy for metastatic/advanced disease, and thus they can participate in the study
• Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication
• Have unresolved or unstable serious toxicity (≥ common terminology criteria for adverse events \[CTCAE\] 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior cancer treatment
• Have a known positive test for human immunodeficiency virus, hepatitis C (treatment naïve or after treatment without sustained virologic response), or hepatitis B infection with hepatitis B virus deoxyribonucleic acid exceeding 2000 IU/mL
• Have a known history of drug addiction within last 1 year which, in the opinion of the Investigator, could increase the risk of non-compliance to investigational product
• Need continuous treatment with proton pump inhibitors during the study period

Sponsors & Collaborators

• ASLAN Pharmaceuticals: lead
• bioRASI, LLC: collaborator
• CMIC Co, Ltd. Japan: collaborator
• Syneos Health: collaborator

Study Sites (21)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Karmanos Cancer Institute/Wayne State University

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

CCCN

Las Vegas, Nevada, 89169, United States

Location

Ruttenberg Cancer Center, Mount Sinai Hospital

New York, New York, 10029, United States

Location

Levine Cancer Institute, Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 12221, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

There are 5 sites in different cities in Australia

Camperdown, Australia

Location

There are 6 sites in different cities in China

Nanjing, Nanjing, 210031, China

Location

There are 2 sites in Hong Kong

Hong Kong, Hong Kong

Location

There are 2 sites in Hungary

Budapest, 1062, Hungary

Location

There are 7 sites in different cities in Japan

Chiba, Japan

Location

There are 2 sites in different cities in Poland

Otwock, 05-400, Poland

Location

There are 2 sites in Singapore.

Singapore, 169610, Singapore

Location

There are 15 sites in different cities in South Korea

Seoul, South Korea

Location

There are 5 sites in different cities in Spain

Barcelona, 08035, Spain

Location

There are 5 sites in different cities in Taiwan

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Neoplasms; Bile Duct Neoplasms; Gallbladder Neoplasms

Interventions

ARRY-334543; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Bile Duct Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Study Director
• Organization: ASLAN Pharmaceuticals

contact@aslanpharma.com

+65 6222 4235

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: March 28, 2017
• Study Start: July 4, 2017
• Primary Completion: November 12, 2019
• Study Completion: April 17, 2020
• Last Updated: August 3, 2021
• Results First Posted: August 3, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); HK (1); CN (1); ES (1); AU (1); HU (1); PL (1); SG (1); KR (1); TW (1); JP (1)