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ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy

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ClinicalTrials.gov Identifier: NCT02609958
Recruitment Status : Completed
First Posted : November 20, 2015
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Aslan Pharmaceuticals

Brief Summary:

This is a single arm, multicentre, Phase 2 study to assess efficacy and safety of ASLAN001 in patients with advanced or metastatic cholangiocarcinoma who progressed on at least 1 line of systemic therapy.

25 evaluable patients will be enrolled in the study. After evaluation of initial response in the first 10 evaluable patients, Sponsor will make a decision on recruitment of an additional 15 evaluable patients. If no response is observed, the study will stop.

The primary objective is to assess efficacy of varlitinib (also known as ASLAN001) as measured by ORR (based on RECIST v1.1). The secondary objectives are to (1) evaluate the efficacy of varlitinib, as measured by DoR, PFS, OS and DCR, (2) assess ORR, DoR, PFS, DCR and OS by tumor EGFR/HER2 status, (3) assess safety and tolerability of ASLAN001 monotherapy. Exploratory objectives are to explore possible relationships between response to ASLAN001 and the protein expression levels and gene mutational status of the proteins and genes via IHC and PCR/Sequencing.


Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Drug: Varlitinib Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2A, Single Arm, Multicentre, Study of ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy
Actual Study Start Date : November 16, 2015
Actual Primary Completion Date : July 7, 2017
Actual Study Completion Date : October 11, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Arm A
Varlitinib (ASLAN001) tablets
Drug: Varlitinib

varlitinib tablets with:

  1. starting dose: 300mg BID
  2. target dose: 400mg BID
  3. dose modification by investigator allowed between 200mg BID to 500mg BID
Other Names:
  • ASLAN001
  • ARRY-334543
  • ARRY-543




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Through study duration, estimated 3 years ]
    Defined as the proportion of patients with a response of PR or CR, as defined by RECIST v1.1 criteria. Data obtained up until disease progression, or last evaluable assessment in the absence of disease progression, will be included in the assessment of ORR.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Through study duration, estimated 3 years ]
    PFS is 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) regardless of whether the patient withdraws from study therapy or receives another antitumour therapy prior to disease progression.

  2. Disease Control Rate (DCR) [ Time Frame: Through study duration, estimated 3 years ]
    Defined as proportion of patients with a best response of stable disease or better as defined by RECIST v1.1 criteria. Note, a minimum interval of 6 weeks (±5 days) from first dose is required for a patient to be attributed a best response of stable disease. Data obtained up until disease progression, or last evaluable assessment in the absence of disease progression, will be included in the assessment of DCR.

  3. Duration of Response (DoR) [ Time Frame: Through study duration, estimated 3 years ]

    Defined as the time from the date of first documented response until the date of documented disease progression or death in the absence of disease progression, the end of response should coincide with the date of disease progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR.

    If a patient does not progress following a response, then their DoR will use the PFS censoring time.


  4. Overall Survival (OS) [ Time Frame: Through study duration, estimated 3 years ]
    Defined as the time from the date of start of treatment until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

  5. Safety for all advanced or metastatic Cholangiocarcinoma (CCA) subjects (Physical examination, vital signs, weight, ECG parameter, clinical laboratory tests and Adverse Events) [ Time Frame: Through study duration, estimated 3 years ]
    Patient safety will be evaluated based on physical examination, vital signs (blood pressure [systolic and diastolic], resting pulse, respiratory rate, weight and body temperature), ECG parameters, clinical laboratory tests (hematology, clinical chemistry, coagulation and urinalysis) and AEs.


Other Outcome Measures:
  1. Possible relationship of protein expression level and gene mutational status determined from archival material or biopsy tissue samples with response to ASLAN001. [ Time Frame: Through study duration, estimated 3 years ]
    Possible relationship of protein expression level and gene mutational status determined from archival material or biopsy tissue samples with response to ASLAN001, using IHC, PCR/Sequencing and if additional material is available, IHC staining methods.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have advanced (unresectable) or metastatic, intra or extra hepatic adenocarcinoma originated from bile duct. Histologically-confirmed diagnosis is required for the first 10 evaluable patients. The following patients could be confirmed histologically or cytologically.
  • Patients must have disease progression after failing at least 1 line of systemic drug regimen for advanced cholangiocarcinoma due to disease progression or intolerance.
  • Presence of radiographically measurable disease based on RECIST v1.1.
  • 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).
  • Patients of respective country's legal age or older at the time of written informed consent.
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Patient must be able to understand and willing to sign the informed consent form and donate tumour tissue (archival or fresh) for evaluation of relevant exploratory endpoints. The first 10 evaluable patients need to have adequate archival tissues for exploratory objectives.
  • Patient with adequate organ and hematological function:

    • Hematological function, as follows:

      • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
      • Platelet count ≥ 100 x 10^9/L
    • Renal functions, as follows:

      ---Serum creatinine ≤ 1.5x ULN or eGFR > 60 mL/min/1.73m^2

    • Hepatic function, as follows:

      • Total bilirubin ≤ 1.5 x ULN
      • AST and ALT ≤ 5 x ULN

Exclusion Criteria:

  • Patient with radiation or local treatment within the past 6 weeks for the target lesion(s).
  • Patients with major surgical procedures within 21 days prior to study entry.
  • Patient with brain lesion, known brain metastases (unless previously treated and well controlled for a period of at least 3 months).
  • Patient with malabsorption syndrome, diseases significantly affecting gastrointestinal function, resection of the stomach or small bowel, or difficulty in swallowing and retaining oral medications.
  • 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 any history of other malignancy unless in remission for more than 1 year. (Nonmelanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
  • Female patients who are pregnant or breast feeding.
  • Patients who were previously treated with Varlitinib.
  • 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.
  • Patient with unresolved or unstable serious toxicity ( ≥ CTCAE 4.03 Grade 2) from prior administration of another investigational drug and/or prior cancer treatment.
  • Patients with a known history of HIV, decompensated cirrhosis, chronic hepatitis B with HBV DNA > 2000 IU/ml or persistent abnormal ALT in the past 6 months, chronic hepatitis C with persistent abnormal ALT in the past 6 months.
  • Known History of drug addiction within last 1 year.
  • Patients who need continuous treatment with proton pump inhibitors during the study period.
  • 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.

For additional information regarding investigative sites for this trial, pls contact ASLAN at contactus@aslanpharma.com


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02609958


Locations
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Korea, Republic of
Seoul, Korea, Republic of
Singapore
Singapore, Singapore
Taiwan
Taipei, Taiwan
Sponsors and Collaborators
Aslan Pharmaceuticals
Investigators
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Study Director: Please contact us for more information ASLAN Pharmaceuticals Pte Ltd

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Responsible Party: Aslan Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02609958     History of Changes
Other Study ID Numbers: ASLAN001-005
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
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Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms