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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03604679
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
SymBio Pharmaceuticals

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

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Study Type : Interventional
Estimated Enrollment : 96 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
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine


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




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03604679


Contacts
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Contact: Shiho Takeda (+81)3-5472-1127 stakeda.st01@symbiopharma.com

Locations
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Japan
Research Site Recruiting
Chuo-ku, Tokyo, Japan
Research Site Recruiting
Osakasayama, Japan
Sponsors and Collaborators
SymBio Pharmaceuticals
Investigators
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Study Director: Akio Hayashi SymBio Pharmaceuticals
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Responsible Party: SymBio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03604679    
Other Study ID Numbers: 2017003
First Posted: July 27, 2018    Key Record Dates
Last Update Posted: July 27, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Bendamustine Hydrochloride
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents