SyB C-0501(Oral Bendamustine) in Patients With Advanced Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SyB C-0501 SyB C-0501 (Oral Bendamustine) will be administered orally once a day (specified dose). The treatment period of 21 days (Cohort 1; 7 days of administration + 14 days of observation or Cohort 2; 14 days of administration + 7 days of observation or Cohort 3; 21 days of administration) constitutes 1 cycle. Part 1: dose escalation to determine MTD, RD and dosing schedule Part 2: dose expansion at RD |
Drug: SyB C-0501
Specified dose on specified days
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Adverse Events (Types, Incidence, Severity, Relationship to SyB C-0501) [Approximately 4 years]
- Change of laboratory test values and clinical laboratory abnormal values (Incidence, Severity) [Approximately 4 years]
- 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)]
- 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)]
- 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]
- Change of laboratory test values and clinical laboratory abnormal values (Incidence, Severity) [Approximately 2 years]
- Objective Response Rate (ORR), Clinical benefit rate (CBR) and Progression-Free Survival (PFS) [Approximately 2 years]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Chuo-ku, Tokyo | Japan | ||
| 2 | Research Site | Osakasayama | Japan |
Sponsors and Collaborators
- SymBio Pharmaceuticals
Investigators
- Study Director: Katsuhisa Goto, SymBio Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017003