A phase 1 trial of OPB-171775 in patients with advanced or metastatic malignant solid tumors

JRCT ID: jRCT2031200206

Registered date:18/11/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: advanced or metastatic malignant solid tumors
• Date of first enrollment: 06/11/2020
• Target sample size: 36
• Study type: Interventional

Intervention(s)

OPB-171775 will be administered orally once daily on consecutive days for 28 days or twice daily on consecutive days for 28 days (BID regimen). This constitutes 1 cycle. In the pharmacokinetic investigation part, OPB-171775 will also be administered on Day 1 of the single-dose period in Cycle 1. In the dose-escalation part, for the BID regimen, the IMP will also be administered once in the morning of Cycle 1 Day 29.
OPB-171775 will be administered at a daily dose of 0.3 mg in the pharmacokinetic investigation part and daily doses of 0.6, 1, 2, 4, and 6 mg in the dose-escalation part.

Outcome(s)

• Primary Outcome: Dose-limiting toxicity

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Presence of histologically or cytologically confirmed solid cancer.
2) No appropriate treatment option available.
3) Aged 20 years or older at the time of informed consent.
4) Confirmed to have adequate organ function according to laboratory tests at screening.
[Hematopoietic function]
Neutrophil count: >= 1,500/microL
Platelet count: >= 100,000/microL
Hemoglobin: >= 9 g/dL
(with no administration of granulocyte-colony stimulating factor agent or blood transfusion within 14 days before blood sampling)
[Renal function]
Serum creatinine: =< 1.5 times the upper limit of normal (ULN), or Creatinine clearance: >= 50 mL/min (calculated according to the standard formula used at the site)
[Hepatic function]
Total bilirubin: =< 2.5 times the ULN
Aspartate aminotransferase and alanine aminotransferase: =< 2.5 times the ULN (or =< 5 times if liver metastasis is present)
5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
6) A basic rhythm of sinus rhythm, with a resting heart rate of 50 to 100 beats/minute.

Exclude criteria

1) Any of the following cardiovascular risks.
a) Concurrent or historical myocardial infarction
b) Concurrent angina pectoris
c) Presence of an implanted stent for ischemic heart disease and taking at least 2 antiplatelet or anticoagulant drugs
d) Concurrent or historical cardiac failure (cardiac failure classification stage C or D based on the Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Failure [JCS 2017/JHFS 2017])
e) Left ventricular ejection fraction <53%
f) QT corrected by Fridericia's formula > 480 msec at screening
g) Concurrent moderate or worse (or, in the case of the tricuspid valve, severe or worse) valvulopathy
h) A history of open heart surgery
i) Pericardial effusion requiring treatment
j) Atrial fibrillation, arrhythmia requiring treatment, or tachycardia
k) A history of irradiation of the esophagus, heart, or mediastinum for which an effect on the heart cannot be ruled out
l) Concurrent uncontrolled hypertension or diabetes mellitus
m) Having received a cumulative anthracycline anticancer drug dose of >= 500 mg/m2 (adriamycin equivalent dose)
2) A history of resection of the gastrointestinal tract affecting absorption of the IMP in the gastrointestinal tract.
3) Historical or concurrent clinically significant lung disease (such as interstitial lung disease or obstructive lung disease).
4) Infection requiring systemic treatment or pyrexia with a body temperature >= 38 degrees Celsius.
5) Clinically symptomatic metastases to the brain.
6) Having undergone surgery, radiotherapy, chemotherapy, immunotherapy, other treatment for malignant tumor, or treatment with another IMP within 14 days before the start of IMP administration.
7) A history of intracranial hemorrhage, or concurrent bleeding (such as hemophilia, capillary fragility, gastrointestinal hemorrhage, urinary tract hemorrhage, hematemesis, or vitreous hemorrhage).
8) Adverse events due to prior treatment that have not resolved to grade 1 or lower (excluding hemoglobin level, alopecia, peripheral nerve disorder, and pigmentation).
9) Hepatitis B virus deoxyribonucleic acid (HBV-DNA) positive, hepatitis C virus (HCV) antibody positive, or human immunodeficiency virus antibody positive.

Related Information

• Primary Sponsor: Headquarters of Clinical Development