NCT03256331TerminatedPhase 1
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
Belx Bio-Pharmaceutical (Taiwan) Corporation2 sites in 1 country23 target enrollmentStarted: June 21, 2017Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 23
- Locations
- 2
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Study Overview
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).
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)
Study Design
- Study Type
- Interventional
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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 m
- •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
- •Child-Pugh Class A; (Score ≤6)
- •Serum albumin ≥2.8 g/dL
- •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
- •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
- •Must have recovered from toxicities of previous anti-cancer treatments to NCI-CTCAE version 4.03 grade 1 or lower, except for alopecia
- •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
- •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
- •Given signed and dated written informed consent and willing/able to comply with all protocol required visits/procedures
Exclusion Criteria
- •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
Arms & Interventions
BEL-X-HG
Experimental
3+3 dose escalation
Intervention: BEL-X-HG (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Oxidative stress(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))
- immunological status(up to 168 days (up to 6 cycles of each enrolled subjects))
- cachexia status(up to 168 days (up to 6 cycles of each enrolled subjects))
- Incidence of Treatment-Emergent Adverse Events(up to 168 days (up to 6 cycles of each enrolled subjects))
- liver function(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))
- Quality of life (QoL) of patients with advanced refractory solid tumors(up to 168 days (up to 6 cycles of each enrolled subjects))
Investigators
Study Sites (2)
Loading locations...
Similar Trials
Withdrawn
Phase 1
Study of PF-07224826, as a Single Agent or in Combination With Endocrine Therapy in Participants With Breast Cancer and Other Advanced Solid Tumors.Non-small Cell Lung Cancer (NSCLC)EndometrialSolid TumorsOvarian CancerLiposarcomaBreast CancerNCT05905341Pfizer
Unknown
Phase 1
A Study to Investigate the Safety of SYHA1815 in Subjects With Unresectable Locally Advanced or Metastatic Solid TumorsLocally Advanced Unresectable CarcinomaNCT05105464Shanghai Runshi Pharmaceutical Technology Co., Ltd97
Recruiting
Phase 1
A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung CancerNon-Small Cell Lung CancerNCT06046495Avistone Biotechnology Co., Ltd.81
Completed
Phase 1
Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Solid TumorsSolid TumorsNCT00942799Genzyme, a Sanofi Company87
Terminated
Phase 1
FHD-286 in Subjects With Metastatic Uveal MelanomaMetastatic Uveal MelanomaNCT04879017Foghorn Therapeutics Inc.76