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

NCT03604679 | Completed Phase 1

• 1 other identifier: 2017003
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Identification of Dose-Limiting Toxicity (DLT) and Number of Subjects with DLT in Each Cohort/Level

  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.

  Cycle 1 (Approximately 3 weeks)

• Adverse Events (Types, Incidence, severity, Relationship to SyB C-0501)

  Approximately 2 years

Secondary Outcomes (12)

• 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)

Study Arms (1)

SyB C-0501

EXPERIMENTAL

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

Interventions

SyB C-0501 DRUG

Specified dose on specified days

Also known as: bendamustine hydrochloride

SyB C-0501

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• SymBio Pharmaceuticals: lead

Study Sites (2)

Research Site

Chuo-ku, Tokyo, Japan

Location

Research Site

Sayama, Japan

Location

Related Publications (1)

• Shimizu T, Nakagawa K, Hayashi H, Iwasa T, Kawakami H, Watanabe S, Yamamoto N, Yonemori K, Koyama T, Sato J, Tamura K, Kikuchi K, Akaike K, Takeda S, Takeda M. Oral formulation of bendamustine hydrochloride for patients with advanced solid tumors; a phase 1 study. Invest New Drugs. 2023 Feb;41(1):1-12. doi: 10.1007/s10637-022-01307-6. Epub 2022 Nov 4.

  PMID: 36331674 DERIVED

MeSH Terms

Interventions

Bendamustine Hydrochloride

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Katsuhisa Goto

  SymBio Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: July 27, 2018
• Study Start: May 24, 2018
• Primary Completion: September 11, 2020
• Study Completion: September 11, 2020
• Last Updated: April 27, 2021

Record last verified: 2021-04

Locations

JP (2)