Clinical trial NCT02347228: Evaluate Safety, Tolerability, PK, Preliminary Clinical Activity of OB318 in Patients With Advanced Solid Malignancies
Official title: A Phase I, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Clinical Activity of OB318 in Patients With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Malignancies
Keywords: OB318
Advanced Solid Malignancies
Antrodia cinnamomea
Antrodia camphorata
Lead sponsor: Oneness Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objectives of this Phase I study are to determine the maximum tolerable dose (MTD) and to evaluate pharmacokinetics (PK), safety/ tolerability and preliminary efficacy of OB318 in patients with advanced solid malignancies.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients of age ≥20 years
2. Pathologically or cytologically confirmed advanced solid tumors for which standard therapy proven to provide clinical benefit does not exist or is no longer effective; the diagnosis of hepatocellular carcinoma (HCC) made according to the imaging specified in the American Association for the Study of Liver Diseases (AASLD) 2018 is acceptable.
3. Evaluable disease, either at least one measurable untreated target lesion on imaging by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria or measurable by informative tumor marker(s).
4. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
5. Life expectancy ≥ 3 months.
6. 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.
7. Must have recovered from toxicities of previous anti-cancer treatments to NCI-CTCAE grade 1 or lower, except for alopecia.
8. Laboratory values at screening of:

   * Absolute neutrophil count ≥ 1,500 /mm3;
   * Platelets ≥ 75,000 /mm3;
   * Hemoglobin (Hb) ≥ 8.5 g/dL;
   * Total bilirubin ≤2.0 mg/dL;
   * AST (SGOT) ≤ 3 × ULN (upper limit of normal);
   * ALT (SGPT) ≤ 3 × ULN;
   * Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance ≥ 60 mL/min.
9. Patients with primary liver cancer or hepatic metastasis are eligible to enroll, provided that, at screening, the following criteria are met:

   * Total bilirubin ≤2.0 mg/dL;
   * AST and ALT ≤ 5 × ULN;
   * Child-Pugh Class A;
   * 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. Female patients must be either of non-childbearing potential, i.e. surgically sterilized or one year post-menopausal; or, if of childbearing potential, confirmed not pregnant at screening and must use adequate contraceptive precautions (as per investigator) during the entire treatment period of this study and for 6 months after exiting from the study.
11. Male patients with female partners of childbearing potential must be willing to use a reliable form of contraception (as per investigator), from screening until 6 months after exiting from the study.
12. 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 grade 1 or less 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, eg., bad nutrition, proteinuria, etc..
5. Previous malignancy, except for basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumor was treated with curative intent more than 2 years prior to study entry.
6. Known allergic to OB318 or its formulation excipients.
7. History of autoimmune disease.
8. Taking anti-coagulant or anti-platelet drugs (eg aspirin, Coumadin, ginko, clopidogrel).
9. Use of any investigational agents or non-registered product within 4 weeks of baseline.
10. Known human immunodeficiency virus (HIV) positivity.
11. With conditions, judged by the investigator, as unsuitable for the study.

Primary outcomes:
measure: Dose limiting toxicities (DLTs) of OB318
timeFrame: 28 days
measure: Maximum tolerated dose (MTD) of OB318
timeFrame: 28 days
Secondary outcomes:
measure: Changes in laboratory safety tests (hematology, biochemistry, urinalysis) from baseline
timeFrame: up to 84 days
measure: Incidence of Adverse Events (AEs)
timeFrame: up to 84 days
measure: Incidence of Serious Adverse events (SAEs)
timeFrame: up to 84 days
measure: Incidence of toxicities ≥ grade 3, according to NCI-CTCAE version 4.03, related to OB318, during extension phase
timeFrame: up to 84 days
measure: Characterization of toxicities ≥ grade 3, according to NCI-CTCAE version 4.03, related to OB318, during extension phase
timeFrame: up to 84 days
measure: Changes in physical examination from baseline
timeFrame: up to 84 days
measure: Changes in vital signs from baseline
timeFrame: up to 84 days
measure: Changes from baseline in Electrocardiogram (ECG) results (QRS, QT, QTc, RR intervals)
timeFrame: up to 84 days
measure: Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at the end of the
timeFrame: up to 84 days
measure: Pharmacokinetic parameters- Cmax
timeFrame: Day 1 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- AUC from time zero to the last quantifiable concentration
timeFrame: Day 1 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- AUC from time zero extrapolated to infinity
timeFrame: Day 1 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters-CL/F
timeFrame: Day 1 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters-Vz/F
timeFrame: Day 1 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters-Tmax
timeFrame: Day 1 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Terminal elimination half-life
timeFrame: Day 1 and Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Terminal elimination rate constant
timeFrame: Day 1 and Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters-Ctrough
timeFrame: Day 27 and Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318 ; Day 7 and Day 14 of Cycle additionally for dose level 1 only
measure: Pharmacokinetic parameters- Cmin,ss
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Cmax,ss
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Cavg,ss
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- AUC(0-24h)
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- CLss/F
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Vz,ss/F
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Tmax,ss
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- FI
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
measure: Pharmacokinetic parameters- Rac
timeFrame: Day 28 of Cycle 1 from the subjects with dose level 1, 2, 4, 6, 8, and 10 of OB318
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University-Shuang Ho Hospital
Study officials:
affiliation: Tri-Service General Hospital
name: Ching-Liang Ho
role: PRINCIPAL_INVESTIGATOR
References: