A Phase 1 interventional study of BEL-X-HG in Advanced Solid Tumors, sponsored by Belx Bio-Pharmaceutical (Taiwan) Corporation. Terminated at 2 sites in Taiwan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2020-06-01.
Sponsored by Belx Bio-Pharmaceutical (Taiwan) Corporation · Phase 1, Interventional, and Treatment
This is a Phase I, open-label, uncontrolled, multicenter dose escalation and extension study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate safety / tolerability and preliminary effects of BEL-X-HG in patients with advanced refractory solid tumors. Dose escalation during the study will be made based on dose-limiting toxicity (DLT).
This study will be carried out in 2 parts:
Part 1: A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose escalation will be made based on dose-limiting toxicity (DLT), for a single cycle (28-days) of BEL-X-HG treatment
Part 2: A Dose Extension Part of up to 5 cycles (28-days each) at the same dose level (starting dose) of BEL-X-HG treatment
Approximately 24-48 eligible subjects with confirmed advanced refractory solid tumors will be enrolled sequentially, in 3 subject cohorts, from the lower to the higher dose cohort into the study. Escalating dose levels of BEL-X-HG in 4 study cohorts and one modified dose will be as follows:
Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid)
Cohort 2: Dose level 2 - 1.0 g/day (0.5 g, bid)
Cohort 3: Dose level 3 - 2.0 g/day (1.0 g, bid)
Cohort 4: Dose level 4 - 4.0 g/day (2.0 g, bid)
Modified dose level Cohort 5: Dose level 5 - 1.5 g/day (0.75g bid) This re-escalation is allowed only when dose de-escalates from Dose level 3 to Dose level 2, and 1 DLT in 6 evaluable subjects of Dose level 2.
BEL-X-HG will be administered orally at the assigned dose level for a single cycle consisting of 28 days during the Dose Escalation Part to each subject. Thereafter, if eligible and willing, subjects can continue to Extension Part for 5 more cycles of treatment (each cycle lasting 28 days), at the same assigned dose level of BEL-X-HG treatment.
Laboratory values at screening and baseline (Day 1) of:
MDRD Study equation: eGFR = 186 x (SCr)\^-1.154 x (age)\^0.203 x (0.742 if female) x (1.210 if African American) SCr: serum creatinine in mg/dL; age: in year
Patients with primary liver cancer or hepatic metastasis are eligible to enroll, provided that, at screening and baseline (Day 1), the following criteria are met:
Exclusion Criteria:
Known hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier who has:
Mean QTc with Fridericia's correction (QTcF*) greater than 450 ms in screening ECG or history of familial long QT syndrome
*: Fridericia's formula:
3+3 dose escalation
Drug: BEL-X-HG
This study will be carried out in 2 parts: 1. A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose escalation will be made based on DLT, for a single cycle (28 days) of BEL-X-HG treatment 2. A Dose Extension Part of up to 5 cycles (28 days each) at the same dose level (starting dose) of BEL-X-HG treatment Escalating dose levels of BEL-X-HG in 5 study cohorts and one modified dose will be as follows: * Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid) * Cohort 2: Dose level 2 - 1.0 g/day (0.5 g, bid) * Cohort 3: Dose level 3 - 2.0 g/day (1.0 g, bid) * Cohort 4: Dose level 4 - 4.0 g/day (2.0 g, bid) Modified dose level Cohort 5: Dose level 5 - 1.5 g/day (0.75g bid) This re-escalation is allowed only when dose de-escalates from Dose level 3 to Dose level 2, and 1 DLT in 6 evaluable subjects of Dose level 2.
Maximum Tolerated Dose (MTD)
The prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).
Time frame: 28 days (first treatment cycle of every subjects)
Incidence of Treatment-Emergent Adverse Events
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST)
Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
Oxidative stress
Oxidative stress
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
nutritional status
serum prealbumin, triglyceride, and total cholesterol
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
immunological status
TNF-alpha, IL-1, IL-2, IL-4, and IL-6
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
cachexia status
fast blood glucose, C-reactive protein, and testosteron
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
Quality of life (QoL) of patients with advanced refractory solid tumors
SF-36 Quality of Life (QoL) Questionnaire
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
liver function
serum AST, ALT, AKP, albumin, gamma-GT, ferritin, PT/INR and APRI
Time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
Plan to share: No
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