Trial Title:
NBM-BMX Administered Orally to Patients With Solid Tumors or Newly Diagnosed Glioblastoma
NCT ID:
NCT06012695
Condition:
Malignant Neoplasm
Malignant Neoplasm of Brain
Conditions: Official terms:
Neoplasms
Glioblastoma
Brain Neoplasms
Temozolomide
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NBM-BMX Capsule
Description:
Each capsule contains 100 mg of the active ingredient.
Arm group label:
combination therapy in newly diagnosed glioblastoma
Arm group label:
monotherapy in advanced solid tumors
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
TMZ will be administered orally at a 75 mg/m2 dose daily during concomitant therapy. In
the maintenance period, days 1-5 of each cycle will be administered 150-200 mg/m2.
Arm group label:
combination therapy in newly diagnosed glioblastoma
Other name:
Temodal® Capsules
Intervention type:
Radiation
Intervention name:
Standard radiotherapy
Description:
A total dose of 60 Gy will be administered in 6 weeks.
Arm group label:
combination therapy in newly diagnosed glioblastoma
Summary:
NBM-BMX is an orally available new chemical entity to inhibit histone deacetylases 8
(HDAC8) activity specifically, being developed as a potential anti-cancer therapeutic by
NatureWise. This study aims to evaluate the safety, pharmacokinetics, and preliminary
efficacy of NBM-BMX as monotherapy in subjects with advanced solid tumors or combination
with the standard of care treatment in subjects with newly diagnosed glioblastoma.
Detailed description:
This is a multi-center, open-label, 2-arm, phase Ib/II study to evaluate the safety,
pharmacokinetics, and preliminary efficacy of NBM-BMX as monotherapy in the treatment of
solid tumors (Arm A) or in combination with radiotherapy/temozolomide in the treatment of
glioblastoma (Arm B).
Arm A consists of dose escalation cohorts in subjects with advanced solid tumors who will
be treated with NBM-BMX monotherapy at different dose levels. Arm B consists of dose
escalation cohorts (Phase Ib) and expansion cohorts (Phase II) in subjects with newly
diagnosed glioblastoma (GBM). Subjects will be treated with NBM-BMX at different dose
levels in combination with the first-line standard of care treatment (i.e., concomitant
Radiotherapy (RT)/TMZ followed by adjuvant TMZ) in Phase Ib. After the recommended Phase
2 dose (RP2D) is determined in Phase Ib, additional subjects will be enrolled and treated
at the RP2D to evaluate the efficacy of NBM-BMX combination therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Arm A (advanced solid tumors)
1. Having signed and dated the informed consent form.
2. Females or males > 18 years old.
3. Histologically or cytologically confirmed advanced solid tumors refractory to
standard of care therapy, or for which no standard of care therapy is available.
4. Disease that is measurable or evaluable as defined by Response Evaluation Criteria
in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology (RANO)
criteria (for CNS tumors).
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
6. Adequate organ function as defined by the following criteria:
1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 ×
upper limits of normal (ULN), unless liver metastases present, then ≤ 5 × ULN
2. Total serum bilirubin ≤ 1.5 × ULN unless bilirubin elevation is related to
Gilbert's Syndrome for which bilirubin ≤ 3 × ULN
3. Absolute neutrophil count (ANC) ≥ 1,000/μL
4. Platelets ≥ 75,000/μL
5. Hemoglobin ≥ 8.0 g/dL
6. Non-indexed estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m2 ×
BSA (m2)/1.73.
Transfusion is not allowed to meet entry criteria.
7. QTcF ≤ 480 msec
8. Willingness and ability to comply with the study scheduled visits, treatment plans,
laboratory tests and other procedures.
Arm B (newly diagnosed GBM)
1. Having signed and dated the informed consent form.
2. Females or males > 18 years old.
3. Newly diagnosed, histologically confirmed glioblastoma, non-resectable, partially
resected or resected.
4. Karnofsky performance status (KPS) ≥ 60 at screening and before the initiation (Day
1) of concomitant therapy.
5. Disease that is measurable or evaluable as defined by Response Assessment in
Neuro-Oncology (RANO) criteria.
6. Adequate organ function as defined by the following criteria:
1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 ×
upper limit of normal (ULN), unless liver metastases present, then ≤ 5 × ULN
2. Total serum bilirubin ≤ 1.5 × ULN unless bilirubin elevation is related to
Gilbert's Syndrome for which bilirubin ≤ 3 × ULN
3. Absolute neutrophil count (ANC) ≥ 1,500/μL
4. Platelets ≥ 100,000/μL
5. Hemoglobin ≥ 8.0 g/dL
6. Non-indexed estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 ×
BSA (m2)/1.73.
Transfusion is not allowed to meet entry criteria.
7. QTcF ≤ 480 msec
8. Willingness and ability to comply with the study scheduled visits, treatment plans,
laboratory tests and other procedures.
Exclusion Criteria:
Arm A (advanced solid tumors)
1. Systemic anti-cancer treatment (investigational or approved) within 28 days or 5
half-lives of that drug (whichever is shorter) of the first dose of NBM-BMX.
2. Curative radiation therapy within 28 days or palliative RT within 7 days of the
first dose of NBM-BMX.
3. Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
4. Any of the following within 6 months of the first dose of NBM-BMX: pulmonary
embolism events, deep vein thrombosis (DVT) events, myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart
failure, or cerebrovascular accident including transient ischemic attack.
5. A positive test for hepatitis B (HBsAg) and/or hepatitis C (anti-HCV antibody),
unless the HBV DNA level and/or HCV RNA level is below the limit of detection.
6. Known history of human immunodeficiency virus (HIV) infection.
7. Men and women of childbearing potential who are unwilling to use highly effective
contraceptive methods during the study period.
Highly effective contraceptive methods include implants, injectables, combined oral
contraceptives, intra-uterine devices (IUDs), sexual abstinence, surgical
sterilization or a partner who is sterile.
8. Females who are pregnant or breastfeeding.
9. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that would impart, in the judgement of the investigator and/or sponsor,
excess risks associated with study participation or study drug administration.
Arm B (newly diagnosed GBM)
1. Prior systemic therapy (including Gliadel wafer implant), immunotherapy,
investigational agents, or radiotherapy for glioblastoma.
2. Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
3. Corticosteroid use of > 8 mg/day dexamethasone or equivalent within 5 days before
the first dose of NBM-BMX.
4. A history of hypersensitivity reaction to temozolomide or dacarbazine.
5. Any of the following within 6 months of the first dose of NBM-BMX: pulmonary
embolism events, deep vein thrombosis (DVT) events, myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart
failure, or cerebrovascular accident including transient ischemic attack.
6. A positive test for hepatitis B (HBsAg) and/or hepatitis C (anti-HCV antibody),
unless the HBV DNA level and/or HCV RNA level is below the limit of detection.
7. Known history of human immunodeficiency virus (HIV) infection. Note: HIV testing is
not required.
8. Men and women of childbearing potential who are unwilling to use highly effective
contraceptive methods during the study period and for at least 6 months after the
final dose of temozolomide.
Highly effective contraceptive methods include implants, injectables, combined oral
contraceptives, intra-uterine devices (IUDs), sexual abstinence, surgical
sterilization or a partner who is sterile.
9. Female who are pregnant or breastfeeding.
10. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that would impart, in the judgement of the investigator and/or sponsor,
excess risks associated with study participation or study drug administration.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hualien Tzu Chi Hospital
Address:
City:
Hualien City
Zip:
970
Country:
Taiwan
Status:
Not yet recruiting
Contact:
Last name:
Tsung-Lang Chiu, M.D.
Phone:
+886 3 8561825
Facility:
Name:
Kaohsiung Medical University Chung-Ho Memorial Hospital
Address:
City:
Kaohsiung City
Zip:
807
Country:
Taiwan
Status:
Not yet recruiting
Contact:
Last name:
Ann-Shung Lieu, M.D.
Phone:
+886 7 3121101
Facility:
Name:
Taichung Veterans General Hospital
Address:
City:
Taichung City
Zip:
407
Country:
Taiwan
Status:
Not yet recruiting
Contact:
Last name:
Wen-Yu Cheng, M.D.
Phone:
+886 4 23592525
Facility:
Name:
Koo Foundation Sun Yat-Sen Cancer Center
Address:
City:
Taipei City
Zip:
112
Country:
Taiwan
Status:
Not yet recruiting
Contact:
Last name:
Chi-Feng Chung, M.D.
Phone:
+886 2 28970011
Facility:
Name:
Linkou Chang-Gung Memorial Hospital
Address:
City:
Taoyuan City
Zip:
333
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Kuo-Chen Wei, M.D.
Phone:
+886 3 3281200
Start date:
August 11, 2023
Completion date:
September 30, 2029
Lead sponsor:
Agency:
Novelwise Pharmaceutical Corporation
Agency class:
Industry
Source:
Novelwise Pharmaceutical Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06012695
