Advanced Solid Tumor
Conditions
Brief summary
This study is an open-label, multicenter, phase 1 study of SyB C-0501 by continuous daily oral administration in patients with advanced solid tumors, who have previously received anticancer therapy and consists of two parts. Part 1 is a dose escalation study to evaluate tolerability of SyB C-0501 in the patients, and to find the maximum tolerated dose (MTD), recommended dose (RD) and optimum dosing schedule. Part 2 is being done to evaluate safety and anti-tumor activity of SyB C-0501 preliminarily at RD, and to assess its target cancer exploratory.
Interventions
DRUGSyB C-0501
Specified dose on specified days
Sponsors
SymBio Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 20 years of age or greater at the time of informed consent * Part 1: Patients with histologically or cytologically confirmed advanced solid tumors refractory to standard therapies or without standard therapies. * Part 2: patients with advanced solid tumors\* refractory to standard therapies or without standard therapies. * \*metastatic breast cancer, small cell lung cancer and other tumors decided based on the Part 1 results * ECOG performance status 0-1 * Patients with adequate bone marrow, liver, renal, cardiac and pulmonary function as assessed by the following: * Absolute neutrophil count (ANC) ≥ 1500/μL, who has not received supportive care of treatment with GCS within 2 weeks before the entry * Platelet count ≥ 100,000/μL and Hemoglobin ≥ 9g/dL in patients received no blood transfusions within 2 weeks before the study entry * Serum creatinine ≤ 1.5 x upper limit normal (ULN) or estimated creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation * Serum total bilirubin ≤ 1.5 x ULN in patients not suffering from Gilbert's syndrome * ALT and AST ≤ 3.0 x ULN (≤ 5.0 x ULN if liver lesions) * 12-lead ECG normal * LVEF ≥ 55% by echocardiography * SpO2 ≥ 95% or PaO2 ≥ 65mmHg * Acute toxicity in prior treatment has recovered to baseline or CTCAE Grade 0-1 except the adverse events that, in the judgment of the investigator or sub-investigator, would not provide safety risks in the study. * Serum/urine pregnancy tests performed before the study entry are negative. * Male and female patients of childbearing potential should give their consent to use adequate contraceptive measures during the study and 180 days after completing study treatment. * Provision of written, signed and dated informed consent by the patient or legally acceptable representative after the receipt of adequate information regarding the study * Ability to understand participation in the study, visiting/treatment plan, sampling/analyses and other study procedures; and willingness to follow them
Exclusion criteria
* Active, uncontrollable or symptomatic metastatic tumors in CNS * Complications of interstitial lung disease, pulmonary fibrosis and emphysema diagnosed by chest-X ray or CT scan * Medical history of radiation, idiopathic or drug-induced pneumonitis * Major surgery within 4 weeks before study entry or planning it within 4 weeks * Treatment with immunotherapy, therapeutic antibody or biologics within 4 weeks or their 5 half-lives before study entry, whichever is longer * Treatment with cytocidal chemotherapy or hormonal therapy within 14 days * Radiotherapy within 4 weeks before study entry * Palliative radiotherapy to control metastatic bone pain within 7 days before study entry * Malabsorption syndrome or full/partial gastric resection * Patients intolerable to oral administration in the judgment of the investigator or sub-investigator * Patients under following medical treatment * Anticancer therapy approved for advanced cancers * Study treatment in other clinical trials * Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) detected in blood test * Lactating women * Medical history of allergy to the agents similar to the investigational drug such as alkylating agents or purine nucleoside derivatives * Medical history of allergy to Polyoxyl 40 hydrogenated castor oil or gelatin capsule * Severe acute or chronic physical/mental condition or laboratory abnormalities which could interfere with evaluation of study treatment or results, or which is likely to progress/worsen due to the participation in the study or administration of SyB C-0501 * Any condition that, in the opinion of the investigator or sub-investigator, makes the patient inappropriate for the study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of Dose-Limiting Toxicity (DLT) and Number of Subjects with DLT in Each Cohort/Level | Cycle 1 (Approximately 3 weeks) | Based on the number of patients with DLT and administration dose in each cohort, recommended dosage will be defined for the following clinical phase. A DLT is defined as an adverse event that occurred during the Cycle 1, for which a causality with the investigational products (IP) cannot be ruled out and meets the DLT criteria of this study. |
| Adverse Events (Types, Incidence, severity, Relationship to SyB C-0501) | Approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Maximum concentration (Cmax) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) |
| Time to maximum concentration (tmax) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day15 of Cycle 1 (each cycle is 21 days) |
| Area under the concentration-time curve up to the last time point with detectable plasma concentration (AUC0-last) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) |
| Area under the concentration-time curve up to infinity (AUC0-inf) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) |
| Adverse Events (Types, Incidence, Severity, Relationship to SyB C-0501) | Approximately 4 years |
| Oral clearance (CL/F) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) |
| Apparent volume of distribution (Vd/F) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) |
| Objective Response Rate (ORR), Clinical benefit rate (CBR) and Progression-Free Survival (PFS) | Approximately 4 years |
| Elimination half-life (t1/2) of unchanged bendamustine in plasma | Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) |
| Change of laboratory test values and clinical laboratory abnormal values (Incidence, Severity) | Approximately 4 years |
Countries
Japan
Outcome results
None listed