Evaluate the Safety of BEL-X-HG in Advanced Cancer Patients

NCT03256331 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BELXHG-SP001
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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).

  28 days (first treatment cycle of every subjects)

Secondary Outcomes (8)

• Incidence of Treatment-Emergent Adverse Events

  up to 168 days (up to 6 cycles of each enrolled subjects)

• Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST)

  up to 168 days (up to 6 cycles of each enrolled subjects)

• Oxidative stress

  up to 168 days (up to 6 cycles of each enrolled subjects)

• nutritional status

  up to 168 days (up to 6 cycles of each enrolled subjects)

• immunological status

  up to 168 days (up to 6 cycles of each enrolled subjects)

Study Arms (1)

BEL-X-HG

EXPERIMENTAL

3+3 dose escalation

Drug: BEL-X-HG

Interventions

BEL-X-HG DRUG

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.

BEL-X-HG

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients of age ≥20 years
• Pathologically or cytologically confirmed advanced refractory solid tumors for which standard therapy proven to provide clinical benefit does not exist or is no longer effective. It is acceptable for HCC subjects with Child Pugh stage A to confirm diagnosis of the advanced refractory solid tumors by imaging (CT scan).
• Evaluable disease, at least one measurable target lesion on imaging by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
• Life expectancy ≥ 3 months
• Patients able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major restriction of the stomach or bowels
• Laboratory values at screening and baseline (Day 1) of:
• Absolute neutrophil count (ANC) ≥ 1,500 /mm3
• Platelets ≥ 75,000 /mm3
• Hemoglobin (Hb) ≥ 8.5 g/dL
• Serum creatinine (Cr.) ≤1.5 mg/dL or estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m2.
• 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:
• Total bilirubin (T-Bil) ≤2.0 mg/dL
• AST and ALT ≤ 5 times the institutional upper limit of normal

You may not qualify if:

• Primary major surgery \< 4 weeks prior to the planned first study treatment day
• Lactating or pregnant women or plans to be become pregnant
• Except for alopecia, any drug-related AE from any previous treatments not recovered to NCI-CTCAE version 4.03 grade 1 or lower prior to the planned first study treatment day
• With active systemic infections, active and clinically significant cardiac diseases, active gastrointestinal diseases, active pulmonary diseases, or medical conditions that may significantly affect adequate absorption of investigational product.
• Known allergy to BEL-X-HG or its formulation excipients
• History of autoimmune disease that in the investigator's opinion may be significant to exclude participation in the study
• Use of any investigational agents or non-registered product within 4 weeks of baseline
• Known human immunodeficiency virus (HIV) positivity
• Known hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier who has:
• serum HBV DNA \> 2,000 IU/mL and abnormal ALT (\> 5 ULN) (for HBV carrier)
• abnormal ALT (\> 5 ULN) (for HCV carrier)
• With conditions, judged by the investigator, as unsuitable for the study
• Mean QTc with Fridericia's correction (QTcF\*) greater than 450 ms in screening ECG or history of familial long QT syndrome
• \*: Fridericia's formula:
• Any cancer-directed therapy (chemotherapy, radiotherapy, biological or immunotherapy, etc.) within 4 weeks or 5 half-lives, (whichever is shorter) of baseline

Sponsors & Collaborators

• Belx Bio-Pharmaceutical (Taiwan) Corporation: lead
• A2 Healthcare Taiwan Corporation: collaborator

Study Sites (2)

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Study Officials

• Chia-Chi Lin, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A sequential Dose Escalation Part of four doses following a 3 + 3 design.

Study Record Dates

• First Submitted: August 13, 2017
• First Posted: August 22, 2017
• Study Start: June 21, 2017
• Primary Completion: March 30, 2020
• Study Completion: March 30, 2020
• Last Updated: June 1, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

TW (2)