Status:
COMPLETED
Two-Part, Phase Ib/II, Open Label, Single-Arm, Multi-center Study to Evaluate the Safety and Efficacy of Varlitinib in Combination With Weekly Paclitaxel in EGFR/HER2 Co-expressing Advanced or Metastatic Gastric Cancer Patients
Lead Sponsor:
Yonsei University
Conditions:
Gastric Cancer
Eligibility:
All Genders
19+ years
Phase:
PHASE1
PHASE2
Brief Summary
Phase Ib part of this study determines the recommended phase II dose schedule based on ASLAN001-004 phase Ib (dose-confirmation study of Varlitinib combined with weekly paclitaxel and carboplatin or t...
Detailed Description
This is a two-part, Phase Ib/II, Open label, single arm, multicenter study to determine the maximum tolerated dose (MTD) and the recommended dose schedule of varlitinib in combination with paclitaxel ...
Eligibility Criteria
Inclusion
- Capable of understanding and complying with the requirements of the study and have signed the Informed Consent Form (ICF).
- Able to communicate well with the Investigator and understand and comply with the requirements of the study.
- Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric adenocarcinoma (systemic metastasis or locally advanced unresectable gastric cancer). A subject must have previously received 1st line chemotherapy including fluoropyrimidine and/or platinum and have showed progression.
- Not received paclitaxel-based chemotherapy previously.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1
- Has a measurable or evaluable disease as determined by RECIST 1.1 criteria.
- Able to swallow orally administered medication.
- Life expectancy of at least 3 months
- Has an adequate baseline organ function defined as:
- White blood cells ≥3000/mm3 and neutrophils ≥1500/mm3
- Platelets ≥100000/mm3
- Hemoglobin ≥9.0 g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)
- Total bilirubin ≤2.0 × ULN
- Creatinine≤1.5 × ULN or creatinine clearance (either measured value or estimated value using the Cockcroft-Gault equation) \>60ml/min.
- Part 1, Phase Ib
- Subjects will be included regardless of EGFR and HER-2 Status
- Part 2, Phase II
- 12\. Provision of an unstained, archived tumor tissue sample in a quantity sufficient to allow for central analysis of EGFR and HER2 expression status.
- 13\. Tumours with immunohistochemistry (IHC) evidence of expression of HER1 (at level of +, or ++, or +++) and HER-2 (at level of +, or ++, or +++) using standard criteria. Also, Subjects with HER-2 IHC (at level of +, or ++, or +++) and EGFR gene amplification/ mutation by NGS are included.
Exclusion
- Has multiple cancers (with the exception of completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder cancer, and any other cancers that have not recurred for at least 5 years)
- Has a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed on imaging (preferably CT) or clinical findings
- Has brain or leptomeningeal metastases. Patients may be randomized for the study if they are asymptomatic and require no treatment.
- History of uncontrollable or significant cardiovascular disease meeting any of the following;
- myocardial infarction within 180 days before study enrolment
- uncontrolled angina pectoris within 180 days before study enrolment
- New York Heart Association (NYHA) Class III or IV congestive heart failure
- uncontrolled hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150mmHg or diastolic blood pressure ≥90 mmHg lasting 24 hours or more)
- arrhythmia requiring treatment
- baseline corrected QT interval (Fridericia"s formula) (QTcF) \> 450 ms or patients with known long QT syndrome; torsade de pointes
- Has an active systemic infection requiring treatment.
- Has a contraindication to paclitaxel.
- Has undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment.
- Subjects with malabsorption syndrome, diseases significantly affecting gastrointestinal function, has total gastrectomy, or difficulty in swallowing and retaining oral medications.
- Has received radiotherapy for gastric cancer within 28 days before treatment or radiotherapy for bone metastases within 14 days before treatment
- Positive test result for human immunodeficiency virus-1 (HIV-1) antibody, Hepatitis B surface protein (HBs) antigen and HBV titer\>2000 IU/ml (10,000 copy/ml), or hepatitis C virus (HCV) antibody positive result
- Any unresolved Grade 2 (per CTCAE v4.0) toxicity from previous anti-cancer therapy at the time of enrollment such as neuropathy, except alopecia or anemia
- Previously treated with varlitinib
- Unable to comply to the study protocol
- Have participated in a study involving another investigational drug within 21 days prior to the first dose of study drug
- Has a history of drug hypersensitivity reactions or hypersensitivity to drugs chemically related to the study drug.
Key Trial Info
Start Date :
July 23 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 13 2022
Estimated Enrollment :
27 Patients enrolled
Trial Details
Trial ID
NCT05400915
Start Date
July 23 2019
End Date
June 13 2022
Last Update
November 13 2023
Active Locations (1)
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1
Yonsei University Health System, Yonsei Cancer Center
Seoul, South Korea