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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03256331
Recruitment Status : Terminated (In the light of the on-going COVID-19 pandemic and the resulted difficulty in patient recruitment.)
First Posted : August 22, 2017
Last Update Posted : June 1, 2020
Sponsor:
Collaborator:
A2 Healthcare Taiwan Corporation
Information provided by (Responsible Party):
Belx Bio-Pharmaceutical (Taiwan) Corporation

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).

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: BEL-X-HG Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Sequential Assignment
Intervention Model Description: A sequential Dose Escalation Part of four doses following a 3 + 3 design.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Dose Escalation and Extension Study to Evaluate the Safety, Tolerability and Preliminary Effects of Oral BEL-X-HG in Patients With Advanced Refractory Solid Malignancies
Actual Study Start Date : June 21, 2017
Actual Primary Completion Date : March 30, 2020
Actual Study Completion Date : March 30, 2020

Arm Intervention/treatment
Experimental: BEL-X-HG
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.




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 28 days (first treatment cycle of every subjects) ]
    The prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  2. Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  3. Oxidative stress [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    Oxidative stress

  4. nutritional status [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    serum prealbumin, triglyceride, and total cholesterol

  5. immunological status [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    TNF-alpha, IL-1, IL-2, IL-4, and IL-6

  6. cachexia status [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    fast blood glucose, C-reactive protein, and testosteron

  7. Quality of life (QoL) of patients with advanced refractory solid tumors [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    SF-36 Quality of Life (QoL) Questionnaire

  8. liver function [ Time Frame: up to 168 days (up to 6 cycles of each enrolled subjects) ]
    serum AST, ALT, AKP, albumin, gamma-GT, ferritin, PT/INR and APRI



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:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients of age ≥20 years
  2. 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).
  3. Evaluable disease, at least one measurable target lesion on imaging by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria.
  4. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
  5. Life expectancy ≥ 3 months
  6. 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
  7. 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

  8. 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
    • Child-Pugh Class A; (Score ≤6)
    • Serum albumin ≥2.8 g/dL
  9. Patients with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months
  10. If history of brain metastases treated with radiation therapy, radiation therapy is required to be completed at least 3 months prior to enrolment and metastasis achieve stable disease (SD) since radiation completion
  11. Must have recovered from toxicities of previous anti-cancer treatments to NCI-CTCAE version 4.03 grade 1 or lower, except for alopecia
  12. Females patient must be either of non-childbearing potential, i.e. surgically sterilized (e.g. tubal ligation, hysterectomy, or ovariectomy) or one year post- menopausal; or, if of childbearing potential, confirmed not pregnant at screening and use of two adequate contraceptive precautions (as per investigator) i.e. condoms plus oral contraceptives or condoms plus endometrial contraceptive devices, during the entire treatment period of this study and for 6 months after exiting from the study
  13. Male patients with female partners of childbearing potential must be willing to use a reliable form of contraception (condoms), from screening until 6 months after existing from the study
  14. Given signed and dated written informed consent and willing/able to comply with all protocol required visits/procedures

Exclusion Criteria:

  1. Primary major surgery < 4 weeks prior to the planned first study treatment day
  2. Lactating or pregnant women or plans to be become pregnant
  3. 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
  4. 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.
  5. Known allergy to BEL-X-HG or its formulation excipients
  6. History of autoimmune disease that in the investigator's opinion may be significant to exclude participation in the study
  7. Use of any investigational agents or non-registered product within 4 weeks of baseline
  8. Known human immunodeficiency virus (HIV) positivity
  9. 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)
  10. With conditions, judged by the investigator, as unsuitable for the study
  11. Mean QTc with Fridericia's correction (QTcF*) greater than 450 ms in screening ECG or history of familial long QT syndrome

    *: Fridericia's formula:

  12. Any cancer-directed therapy (chemotherapy, radiotherapy, biological or immunotherapy, etc.) within 4 weeks or 5 half-lives, (whichever is shorter) of baseline

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): NCT03256331


Locations
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Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan, 704
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
Belx Bio-Pharmaceutical (Taiwan) Corporation
A2 Healthcare Taiwan Corporation
Investigators
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Principal Investigator: Chia-Chi Lin, MD, PhD National Taiwan University Hospital
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Responsible Party: Belx Bio-Pharmaceutical (Taiwan) Corporation
ClinicalTrials.gov Identifier: NCT03256331    
Other Study ID Numbers: BELXHG-SP001
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No