SyB C-0501(Oral Bendamustine) in Patients With Advanced Solid Tumors

A Multicenter, Open-label, Phase I Study of SyB C-0501(Oral Bendamustine) in Patients With Advanced Solid Tumors:

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.

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.