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

• ClinicalTrials.gov Identifier: NCT03604679
• Recruitment Status: Completed
• First Posted: July 27, 2018
• Last Update Posted: April 27, 2021
• Sponsor: SymBio Pharmaceuticals
• Information provided by (Responsible Party): SymBio Pharmaceuticals

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
Advanced Solid Tumor	Drug: SyB C-0501	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Phase I Study of SyB C-0501(Oral Bendamustine) in Patients With Advanced Solid Tumors:
• Actual Study Start Date: May 24, 2018
• Actual Primary Completion Date: September 11, 2020
• Actual Study Completion Date: September 11, 2020

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 Name: bendamustine hydrochloride

Outcome Measures

Primary Outcome Measures :

1. Identification of Dose-Limiting Toxicity (DLT) and Number of Subjects with DLT in Each Cohort/Level [ Time Frame: 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.
2. Adverse Events (Types, Incidence, severity, Relationship to SyB C-0501) [ Time Frame: Approximately 2 years ]

Secondary Outcome Measures :

1. Adverse Events (Types, Incidence, Severity, Relationship to SyB C-0501) [ Time Frame: Approximately 4 years ]
2. Change of laboratory test values and clinical laboratory abnormal values (Incidence, Severity) [ Time Frame: Approximately 4 years ]
3. Maximum concentration (Cmax) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) ]
4. Time to maximum concentration (tmax) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day15 of Cycle 1 (each cycle is 21 days) ]
5. Area under the concentration-time curve up to the last time point with detectable plasma concentration (AUC0-last) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) ]
6. Area under the concentration-time curve up to infinity (AUC0-inf) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) ]
7. Elimination half-life (t1/2) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) ]
8. Oral clearance (CL/F) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) ]
9. Apparent volume of distribution (Vd/F) of unchanged bendamustine in plasma [ Time Frame: Day 1, and Day 8 or Day 15 of Cycle 1 (each cycle is 21 days) ]
10. Objective Response Rate (ORR), Clinical benefit rate (CBR) and Progression-Free Survival (PFS) [ Time Frame: Approximately 4 years ]
11. Change of laboratory test values and clinical laboratory abnormal values (Incidence, Severity) [ Time Frame: Approximately 2 years ]
12. Objective Response Rate (ORR), Clinical benefit rate (CBR) and Progression-Free Survival (PFS) [ Time Frame: Approximately 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Japan

Research Site

Chuo-ku, Tokyo, Japan

Research Site

Osakasayama, Japan

Sponsors and Collaborators

SymBio Pharmaceuticals

Investigators

• Study Director: Katsuhisa Goto; SymBio Pharmaceuticals

More Information

• Responsible Party: SymBio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03604679
• Other Study ID Numbers: 2017003
• First Posted: July 27, 2018
• Last Update Posted: April 27, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Bendamustine Hydrochloride; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents