A Phase 2 Study of Varlitinib Plus Capecitabine in Patients With Advan

A Phase 2 Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic BTC

https://clinicaltrials.gov/ct2/show/NCT03129074

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Purpose
The purpose of the study is to assess the efficacy of varlitinib in combination with capecitabine as measured by objective response rate (ORR) assessed by independent central review (ICR), based on RECIST v1.1 criteria.

Condition Intervention Phase
Advanced or Metastatic Biliary Tract Cancer
Drug: Varlitinib
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 2, Single Arm Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as First-line Systemic Therapy

Resource links provided by NLM:

Drug Information available for: Capecitabine
Genetic and Rare Diseases Information Center resources: Biliary Tract Cancer
U.S. FDA Resources

Further study details as provided by Aslan Pharmaceuticals:

Primary Outcome Measures:
Objective Response Rate (ORR) [ Time Frame: Through study duration, estimated 3 years ]
Number (%) of patients with at least one visit response of CR or PR. Tumor evaluations will continue until the earlier of disease progression or starting a subsequent anti-cancer therapy.

Biomarker [ Time Frame: Through study duration, estimated 3 years ]
Use NGS/IHC to identify relationships between response to varlitinib and mutations or overexpression in HER receptors and the downstream signaling proteins, as well as, mutations in selected cancer pathways.

Secondary Outcome Measures:
PFS [ Time Frame: Through study duration, estimated 3 years ]
Defined as the time from start of treatment until the date of objective disease progression or death (by any cause in the absence of disease progression).

OS [ Time Frame: Through study duration, estimated 3 years ]
Defined as the time from start of treatment until death by any cause.

DoR [ Time Frame: Through study duration, estimated 3 years ]
Defined as the time, in days, from the first recorded achievement of a response (PR or above) until time of objective disease progression in the subset of patients classified as responders in the assessment of ORR

DCR [ Time Frame: Through study duration, estimated 3 years ]
Defined as the proportion of patients with a best response of stable disease maintained for at least 12 weeks (-5 days), PR or CR as defined by RECIST v1.1 criteria.

ORR [ Time Frame: Through study duration, estimated 3 years ]
Defined as the proportion of patients with a best objective response (BOR) of complete response (CR) or partial response (PR), as assessed by the investigator defined by the RECIST v1.1 criteria.

Incidence of AEs and changes from baseline in safety parameters [ Time Frame: Through study duration, estimated 3 years ]
Incidence of AEs, categorized in accordance to CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests).

Estimated Enrollment: 40
Anticipated Study Start Date: July 2017
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Varlitinib given in combination with capecitabine
PO varlitinib 300 mg BID
PO capecitabine 1000 mg/m2 BID
Drug: Varlitinib
everyday
Drug: Capecitabine
from Day 1 to Day 14 followed by 7-day of rest period, every 21 days.

Detailed Description:
Also to explore the role of biomarkers as predictors of response and clinical benefit with varlitinib
Eligibility

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.
Are able to understand and willing to sign the informed consent form.
Have histologically confirmed diagnoses of relapsed, locally advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and carcinoma of Ampulla of Vater.
Have eligible tumor tissue (archival or fresh) for the evaluation of relevant primary endpoints. (Note: For patients without eligible tumor tissue, a discussion with the sponsor is mandatory).
Have radiographically measurable disease as determined by the investigator based on the RECIST v1.1 criteria.
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 1.5 x upper level of normal (ULN).
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Have an estimated life expectancy of more than 3 months, at the time of screening.
Have adequate organ and hematological function:
Hematological function, as follows:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Platelet count ≥ 100 x 109/L
Renal functions, as follows:
eGFR or CrCl > 50 mL/min/1.73m2
Hepatic function, as follows:
Total bilirubin ≤ 1.5 x ULN
aspartate aminotransferase and alanine aminotransferase ≤ 5 x ULN
Exclusion Criteria:

Have received systemic anti-cancer treatment except (neo-) adjuvant therapy for early stage disease.
Are currently on or have received radiation or local treatment within the past 4 weeks for the target lesion(s), prior to screening.
Had undergone major surgical procedures within 28 days prior to study cycle 1 day 1.
Have a metastatic brain lesion(s), including asymptomatic and well controlled lesion(s).
Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, or difficulty in swallowing and retaining oral medications.
Have any history of other malignancy unless in remission for more than 1 year (skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
Are female patients who are pregnant or breast feeding.
Have been previously treated with varlitinib or capecitabine.
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 (≥ CTCAE 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior anti-cancer treatment.
Have a known positive test for human immunodeficiency virus, active viral hepatitis C, viral hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL.
Have a known history of drug addiction within last 1 year, on the basis of which there could be a higher risk of non-compliance to study treatment.
Need continuous treatment with proton pump inhibitors during the study period.
Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or with a history of interstitial lung disease or current interstitial lung disease.
Have any history or presence of clinically significant condition which in the opinion of the investigator could jeopardize the safety of the patient or the validity of the study results.
Have a baseline corrected QT interval > 450 ms or patients with known long QT syndrome, torsade de pointes, symptomatic ventricular tachycardia, unstable cardiac syndrome in the past 3 months before screening visit, > class 2 NYHA heart failure, > grade 2 CCS angina pectoris, or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, or sotalol methadone.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03129074

Contacts
Contact: ASLAN Pharmaceuticals ASLAN Pharmaceuticals ASLAN Pharmaceuticals contact@aslanpharma.com

Sponsors and Collaborators
Aslan Pharmaceuticals
More Information

Responsible Party: Aslan Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03129074 History of Changes
Other Study ID Numbers: ASLAN001-016
Study First Received: April 21, 2017
Last Updated: April 25, 2017
Individual Participant Data
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 26, 2017