Clinical trial NCT03093870: Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Biliary Tract Cancer
Keywords: Neoplasms
Biliary Tract Neoplasms
Bile Duct Neoplasms
Gallbladder Neoplasms
Lead sponsor: ASLAN Pharmaceuticals
Sponsor class: OTHER
Collaborators: name: bioRASI, LLC
name: CMIC Co, Ltd. Japan
name: Syneos Health
First posted: 2017-03-28
Enrollment: 151
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment: protocol designed to evaluate one or more interventions for treating a disease, syndrome or condition
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

Subjects will be eligible for the study if they:

1. Are of or older than the legal age in the respective countries at the time when written informed consent is obtained
2. 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.
3. 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
4. Have received at least 6 doses of gemcitabine containing treatment in first line (Adjuvant therapy is not regarded as 1st line therapy)
5. 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)
6. 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)
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Are able to understand and willing to sign the informed consent form
9. Have adequate organ and hematological function:

   1. Hematological function, as follows:

      * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
      * Platelet count ≥ 100 × 109/L
   2. Renal functions, as follows:

      • Estimated glomerular filtration rate or creatinine clearance \> 50 mL/min/1.73m2
   3. Hepatic function, as follows:

      * Albumin ≥ 3 g/dL
      * Total bilirubin ≤ 1.5 × ULN
      * Aspartate aminotransferase and alanine aminotransferase ≤ 5 × ULN

Exclusion Criteria:

Subjects will be ineligible for the study if they:

1. Are currently on or have received anti-cancer therapy within the past 3 weeks before receiving the first dose of study medication
2. 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
3. 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.)
4. Have had major surgical procedures within 14 days prior to first dose of study medication
5. Have a known metastatic brain lesion(s), including asymptomatic and well controlled lesion(s)
6. 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
7. 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
8. Have any history of other malignancy unless in remission for more than 1 year (non-melanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary)
9. Are female patients who are pregnant or breast feeding
10. 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
11. Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication
12. 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
13. 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
14. 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
15. Need continuous treatment with proton pump inhibitors during the study period
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
17. Have any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the patient or the validity of the study results
18. Have a baseline corrected QT interval (Fridericia's formula) (QTcF) \> 450 ms or patients with known long QT syndrome; torsade de pointes; symptomatic ventricular tachycardia; an unstable cardiac syndrome in the past 3 months before screening visit; \> class 2 New York Heart Association heart failure; or \> class 2 angina pectoris; or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, sotalol, or methadone. Please also see prohibited medication/therapy (Section 5.4.10.1)

Primary outcomes:
measure: Objective Response Rate (ORR) - Part 1
timeFrame: 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.
measure: Progression-free Survival (PFS) - Part 1
timeFrame: 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:
measure: Object Response Rates (ORR) - Safety Lead-In
timeFrame: 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.
measure: Overall Survival (OS) - Part 1
timeFrame: Time from the date of randomization until death due to any cause, up to 2 years
measure: Overall Survival (OS) - Safety Lead-In
timeFrame: Time from the date of randomization until death due to any cause, up to 2 years
measure: Duration of Response (DoR) - Part 1
timeFrame: 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
measure: Disease Control Rate DCR - Part 1
timeFrame: Number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization.
measure: Tumor Size - Part 1
timeFrame: Week 12
measure: Number of Participants With Clinically Significant Laboratory Tests- Safety Lead-in
timeFrame: Subject screening visit to 28 days post last study drug administration
measure: Number of Participants With Clinically Significant Laboratory Tests - Part 1
timeFrame: Subject screening visit to 28 days post last study drug administration
measure: Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Safety Lead-In
timeFrame: Subject screening visit to 28 days post last study drug administration
measure: Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Part 1
timeFrame: Subject screening visit to 28 days post last study drug administration
measure: Number of Participants With ECG Parameters of Interest - Safety Lead-In
timeFrame: Subject screening visit to 28 days post last study drug administration
measure: Number of Participants With ECG Parameters of Interest - Part 1
timeFrame: Subject screening visit to 28 days post last study drug administration
measure: ECOG Performance Status - Part 1
timeFrame: Subject screening visit to 28 days post last study drug administration
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Detroit
country: United States
facility: Karmanos Cancer Institute/Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: CCCN
state: Nevada
city: New York
country: United States
facility: Ruttenberg Cancer Center, Mount Sinai Hospital
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas Healthcare System
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: There are 5 sites in different cities in Australia
city: Nanjing
country: China
facility: There are 6 sites in different cities in China
state: Nanjing
city: Hong Kong
country: Hong Kong
facility: There are 2 sites in Hong Kong
city: Budapest
country: Hungary
facility: There are 2 sites in Hungary
city: Chiba
country: Japan
facility: There are 7 sites in different cities in Japan
city: Seoul
country: Korea, Republic of
facility: There are 15 sites in different cities in South Korea
city: Otwock
country: Poland
facility: There are 2 sites in different cities in Poland
city: Singapore
country: Singapore
facility: There are 2 sites in Singapore.
city: Barcelona
country: Spain
facility: There are 5 sites in different cities in Spain
city: Taipei
country: Taiwan
facility: There are 5 sites in different cities in Taiwan
Study officials:
References: