Clinical Trials /

A Safety and Pharmacokinetic Study of NBM-BMX Administered Orally to Patients With Advanced Cancer

NCT03726294

Description:

NBM-BMX is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by NatureWise. NBM-BMX is a histone deacetylase (HDAC) inhibitor and has been shown to be particularly active against HDAC8. The objectives of this study are to determine the safety profile of NBM-BMX, including identification of dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and to determine the Recommended Phase 2 Dose (RP2D).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Pharmacokinetic Study of NBM-BMX Administered Orally to Patients With Advanced Cancer
  • Official Title: A Phase 1, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Efficacy of NBM-BMX in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: NBM-BMX-001
  • NCT ID: NCT03726294

Conditions

  • Malignant Neoplasm

Interventions

DrugSynonymsArms
NBM-BMX softgel capsulesNBM-BMX

Purpose

NBM-BMX is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by NatureWise. NBM-BMX is a histone deacetylase (HDAC) inhibitor and has been shown to be particularly active against HDAC8. The objectives of this study are to determine the safety profile of NBM-BMX, including identification of dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and to determine the Recommended Phase 2 Dose (RP2D).

Trial Arms

NameTypeDescriptionInterventions
NBM-BMXExperimental
  • NBM-BMX softgel capsules

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed advanced, non-resectable, and/or metastatic
             solid tumor refractory to standard of care therapy, or for whom no standard of care
             therapy is available, or who were not amenable to established forms of treatment.

          2. Solid tumors must have measurable or evaluable disease as per Response Evaluation
             Criteria in Solid Tumors (RECIST) 1.1.

          3. Female or male at 18 years of age or older.

          4. ECOG performance status 0 to 2.

          5. Recovered from prior treatment-related toxicity to at least grade 1 with exception of
             grade 2 alopecia or other grade 2 toxicity with prior approval of the Medical Monitor.

          6. Adequate organ function as defined by the following criteria:

               -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤3 x
                  upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function
                  abnormalities are due to underlying malignancy

               -  Total serum bilirubin ≤1.5 x ULN (except for subjects with documented Gilbert's
                  syndrome)

               -  Absolute neutrophil count (ANC) ≥ 1500/μL

               -  Platelets ≥ 90,000/μL

               -  Hemoglobin ≥ 9.0 g/dL

               -  Serum creatinine ≤1.5 x ULN or creatinine clearance of ≥ 60 mL/min

          7. Signed and dated informed consent document indicating that the subject (or legally
             acceptable representative) has been informed of all the pertinent aspects of the trial
             prior to enrollment.

          8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

        Exclusion Criteria:

        Subjects presenting with any of the following will not be included in the trial:

          1. Major surgery or radiation therapy within 28 days of starting study treatment.

          2. Systemic anti-cancer therapy within 28 days or 5 half-lives (whichever is shorter) of
             starting study treatment.

          3. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.

          4. Current treatment on another clinical trial.

          5. Spinal cord compression, carcinomatous meningitis, or leptomeningeal disease unless
             appropriately treated and neurologically stable for at least 4 weeks.

          6. Any of the following within the 12 months prior to starting study treatment:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, congestive heart failure, or cerebrovascular accident including transient
             ischemic attack; within 6 months prior to starting study treatment for pulmonary
             embolus. However, upon agreement between the investigator and sponsor, the 6 month
             post-event-free period for a subject with a pulmonary embolus can be waived if due to
             advanced cancer. Appropriate treatment with anticoagulants is permitted.

          7. NYHA Class III or IV heart failure and known history of QTc prolongation or Torsade de
             Pointes.

          8. Use of medications known to significantly prolong the QTc interval (e.g.,
             antiarrhythmic and psychotropic medications).

          9. Hypertension that cannot be controlled by medications.

         10. Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO
             daily for deep vein thrombosis prophylaxis is allowed).

         11. Known human immunodeficiency virus (HIV)-positive and is receiving antiretroviral
             therapy. Subjects with known HIV infection and on a stable dose of HIV suppressive
             medication may be eligible if considered to be at low risk for AIDS-related outcomes
             following discussion with the medical monitor.

         12. Known hepatitis B virus (HBV) or hepatitis C virus (HCV) with evidence of chronic
             active disease or receiving/requiring antiviral therapy.

         13. History of receiving organ transplantation or immune disorders that require continuous
             immunosuppressant agent therapy.

         14. Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
             postmenopausal, or must agree to the use of effective contraception during the period
             of therapy. All female subjects with reproductive potential must have a negative
             pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically
             sterile or must agree to use effective contraception during the period of therapy. The
             definition of effective contraception will be based on the judgment of the principal
             investigator or a designated associate.

         15. Other severe acute or chronic medical or psychiatric conditions or laboratory
             abnormalities that would impart, in the judgment of the investigator and/or sponsor,
             excess risk associated with study participation or study drug administration, which
             would make the subject inappropriate for entry into this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity (DLT) of NBM-BMX [Safety and Tolerability]
Time Frame:up to 28 days
Safety Issue:
Description:Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0

Secondary Outcome Measures

Measure:Preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) [Efficacy]
Time Frame:at least 8 weeks
Safety Issue:
Description:
Measure:AUC(0-last) of NBM-BMX [Pharmacokinetics]
Time Frame:Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
Safety Issue:
Description:AUC(0-last): area under the plasma concentration versus time curve to the time of the last measurable concentration
Measure:Cmax of NBM-BMX [Pharmacokinetics]
Time Frame:Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
Safety Issue:
Description:Cmax: maximum plasma concentration
Measure:Tmax of NBM-BMX [Pharmacokinetics]
Time Frame:Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
Safety Issue:
Description:Tmax: time to maximum plasma concentration
Measure:T(1/2) of NBM-BMX [Pharmacokinetics]
Time Frame:Day 1 and 15 for Cycle 1 only (each cycle is 28 days)
Safety Issue:
Description:T(1/2): terminal elimination half-life

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NatureWise Biotech & Medicals Corporation

Last Updated

February 24, 2020