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

NCT05400915 | Completed Phase 1 DMC

• 1 other identifier: 4-2018-1011
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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 trastuzumab (Herceptin) in advanced solid tumours). Phase II part of this study further assesses the safety and clinical efficacy of this combination treatment as a second line treatment in EGFR/HER2 co-expressing advanced or metastatic gastric cancer.

Conditions

Gastric Cancer

Keywords

EGFR/HER2 Co-expressing gastric cancer; Varlitinib

Outcome Measures

Primary Outcomes (3)

• (Phase Ib) Maximum Tolerated dose

  3 years

• (Phase Ib) Dose limiting Toxicity

  3 years

• (Phase II) Progression-free survival

  Progression-free survival (PFS): Defined as the time from start of study treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) Progression is defined in accordance with the RECIST v1.1 criteria.

  3 years

Secondary Outcomes (5)

• Overall Survival

  3 years

• Objective Response Rate

  3 years

• Disease Control Rate

  3 years

• Progression-free survival

  3 years

• Number of Participants With Adverse Events That Are Related to Treatment

  3 years

Study Arms (1)

Variltinib, Paclitaxel

EXPERIMENTAL

Drug: Variltinib, Paclitaxel

Interventions

Variltinib, Paclitaxel DRUG

Varlitinib will be administered orally to the study participants at doses 300mg, BID in combination with the weekly intravenous infusion of Paclitaxel for 3 weeks with a rest period of 1 week.

Variltinib, Paclitaxel

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Yonsei Cancer Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• SUN YOUNG RHA

  Yonsei Cancer Center, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: June 2, 2022
• Study Start: July 23, 2019
• Primary Completion: December 13, 2021
• Study Completion: June 13, 2022
• Last Updated: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)