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A Study of CAN008 for Newly Diagnosed Glioblastoma Multiforme

Primary Purpose

Glioblastoma Multiforme

Status
Completed
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
CAN008
Sponsored by
CANbridge Life Sciences Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Newly diagnosed and histologically confirmed glioblastoma multiforme
  • Tumor must be surgically accessible and tissue must be available
  • Age ≥ 20 years and < 75 years
  • Life expectancy ≥ 6 months
  • Baseline MRI images must be done within 2 days after surgery
  • Patients must have a Karnofsky performances score ≥ 60 prior to treatment.
  • Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
  • Adequate hematologic (absolute neutrophil count (ANC) ≥ 1.5x109/L, platelet count ≥ 100x109/L, hemoglobin ≥ 10 g/dL ), renal (creatinine ≤ 1.25xULN ), and hepatic function (total bilirubin ≤ 1.5xULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN)
  • Women with childbearing potential must have a negative serum pregnancy test less than 7 days prior to the first dose of study drug.
  • Both men and women of reproductive potential agree to use approved contraception, such as condom and placement of an intrauterine device (IUD), during the study and until 3 months after the discontinuation of study treatment.
  • Willing and able to comply with the protocol as judged by the investigator
  • Patients must provide written consent

Exclusion Criteria:

  • Any prior chemotherapy (including carmustine-containing wafers) or immunotherapy (including vaccine therapy )
  • Any prior radiotherapy to the brain
  • Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial
  • Any contraindication to TMZ listed in the local label
  • Low-grade astrocytoma
  • Unable to undergo MRI
  • Past medical history of disease with poor prognosis according to the judgment of the Investigator
  • HIV infection
  • Patients with positive anti-HCV
  • Patients with positive HbsAG who received any related treatment within the past 6 months
  • Patients suffering from hereditary fructose intolerance (HFI).
  • Patients receive any investigational agent(s) or device(s) within 30 days prior to entering the study
  • Known coronary artery disease, significant arrhythmias or severe congestive heart failure

Sites / Locations

  • Chang Gung Memorial Hospital, Linkou
  • National Taiwan University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAN008

Arm Description

CAN008 administered as a 30 min intravenous infusion once a week until disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The safety assessment will include safety laboratory (clinical chemistry, hematology, urinalysis), physical exam, vital signs and 12-lead ECG (QT prolongation). An AE can be any unfavourable and unintended sign, symptom, or disease temporarily associated with the use of a medicinal product, whether or not is considered to be related to the medicinal product. Pre-existing conditions worsen during a study are also to be reported as AEs. Furthermore, any side effects potentially related to the CAN008 treatment will be evaluated.

Secondary Outcome Measures

Recommended Dose for Phase II [RP2D] measured by the Maximum Tolerated Dose [MTD] or the Maximum Administered Dose [MAD]
The RP2D will be determined based on the assessment of the observed toxicities, the maximum tolerated dose (MTD) or the maximum administered dose (MAD), and the overall safety profile of CAN008.
PK profile measured by CAN008 serum concentrations
CAN008 serum concentrations will be determined.
PK profile measured by Maximum Plasma Concentration [Cmax]
Maximum Plasma Concentration [Cmax] will be determined.
PK profile measured by Area Under the Curve [AUC]
Area Under the Curve [AUC] will be determined.
Preliminary efficacy (Progression Free Survival after 6 months [PFS6])
PFS is defined as the time from date of randomization to the date of the event, which is the first radiologically documented disease progression (per local investigator assessment according to Response Assessment in Neuro-Oncology (RANO) criteria) or death due to any cause. For the primary analysis, progression-free survival after 6 months (PFS6) is defined as the crude rate of patients confirmed to be free of progression at 6 months after randomization with respect to the number of randomized and exposed patients in the respective treatment arm.
Preliminary efficacy (Overall Survival [OS])
Overall survival (OS) is defined as the time from the first dose of CAN008 to death.

Full Information

First Posted
July 11, 2016
Last Updated
November 7, 2018
Sponsor
CANbridge Life Sciences Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02853565
Brief Title
A Study of CAN008 for Newly Diagnosed Glioblastoma Multiforme
Official Title
A Phase I Study of CAN008 Plus Concomitant Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 2016 (undefined)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
September 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CANbridge Life Sciences Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To evaluate CAN008 safety, tolerability, and pharmacokinetics (PK) of CAN008 when administered concurrent Plus Concomitant Temozolomide During and After Radiation Therapy in Patients with Newly Diagnosed Glioblastoma Multiforme.
Detailed Description
CAN008 is a glycosylated fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of human IgG1. CAN008 blocks the interaction between CD95 and its cognate ligand CD95L. The target of CAN008 is the inhibition of CD95L. CD95L is expressed in glioblastoma whose cells are resistant to CD95-mediated apoptosis. CD95L was shown to be a crucial trigger in invasion and migration of tumor cells and neutralizing CD95L abolishes the invasive capacity of glioblastoma cells. The purpose of the study is: To describe the toxicity associated with this regimen in adult patients with newly diagnosed glioblastoma multiforme. To determine the duration of disease free survival and overall survival associated with this therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CAN008
Arm Type
Experimental
Arm Description
CAN008 administered as a 30 min intravenous infusion once a week until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
CAN008
Other Intervention Name(s)
APG101
Intervention Description
The dose escalation in the phase I study including 200mg in the first cohort and 400mg in the second cohort to Recommended for Phase 2 Dose (RP2D)
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
The safety assessment will include safety laboratory (clinical chemistry, hematology, urinalysis), physical exam, vital signs and 12-lead ECG (QT prolongation). An AE can be any unfavourable and unintended sign, symptom, or disease temporarily associated with the use of a medicinal product, whether or not is considered to be related to the medicinal product. Pre-existing conditions worsen during a study are also to be reported as AEs. Furthermore, any side effects potentially related to the CAN008 treatment will be evaluated.
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Recommended Dose for Phase II [RP2D] measured by the Maximum Tolerated Dose [MTD] or the Maximum Administered Dose [MAD]
Description
The RP2D will be determined based on the assessment of the observed toxicities, the maximum tolerated dose (MTD) or the maximum administered dose (MAD), and the overall safety profile of CAN008.
Time Frame
up to 2 years
Title
PK profile measured by CAN008 serum concentrations
Description
CAN008 serum concentrations will be determined.
Time Frame
up to 2 years
Title
PK profile measured by Maximum Plasma Concentration [Cmax]
Description
Maximum Plasma Concentration [Cmax] will be determined.
Time Frame
up to 2 years
Title
PK profile measured by Area Under the Curve [AUC]
Description
Area Under the Curve [AUC] will be determined.
Time Frame
up to 2 years
Title
Preliminary efficacy (Progression Free Survival after 6 months [PFS6])
Description
PFS is defined as the time from date of randomization to the date of the event, which is the first radiologically documented disease progression (per local investigator assessment according to Response Assessment in Neuro-Oncology (RANO) criteria) or death due to any cause. For the primary analysis, progression-free survival after 6 months (PFS6) is defined as the crude rate of patients confirmed to be free of progression at 6 months after randomization with respect to the number of randomized and exposed patients in the respective treatment arm.
Time Frame
up to 2 years
Title
Preliminary efficacy (Overall Survival [OS])
Description
Overall survival (OS) is defined as the time from the first dose of CAN008 to death.
Time Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Newly diagnosed and histologically confirmed glioblastoma multiforme Tumor must be surgically accessible and tissue must be available Age ≥ 20 years and < 75 years Life expectancy ≥ 6 months Baseline MRI images must be done within 2 days after surgery Patients must have a Karnofsky performances score ≥ 60 prior to treatment. Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors. Adequate hematologic (absolute neutrophil count (ANC) ≥ 1.5x109/L, platelet count ≥ 100x109/L, hemoglobin ≥ 10 g/dL ), renal (creatinine ≤ 1.25xULN ), and hepatic function (total bilirubin ≤ 1.5xULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN) Women with childbearing potential must have a negative serum pregnancy test less than 7 days prior to the first dose of study drug. Both men and women of reproductive potential agree to use approved contraception, such as condom and placement of an intrauterine device (IUD), during the study and until 3 months after the discontinuation of study treatment. Willing and able to comply with the protocol as judged by the investigator Patients must provide written consent Exclusion Criteria: Any prior chemotherapy (including carmustine-containing wafers) or immunotherapy (including vaccine therapy ) Any prior radiotherapy to the brain Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial Any contraindication to TMZ listed in the local label Low-grade astrocytoma Unable to undergo MRI Past medical history of disease with poor prognosis according to the judgment of the Investigator HIV infection Patients with positive anti-HCV Patients with positive HbsAG who received any related treatment within the past 6 months Patients suffering from hereditary fructose intolerance (HFI). Patients receive any investigational agent(s) or device(s) within 30 days prior to entering the study Known coronary artery disease, significant arrhythmias or severe congestive heart failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ying Xu, MD
Organizational Affiliation
CANbridge Life Sciences Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Chang Gung Memorial Hospital, Linkou
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34911992
Citation
Wei KC, Hsu PW, Tsai HC, Lin YJ, Chen KT, Toh CH, Huang HL, Jung SM, Tseng CK, Ke YX. Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study. Sci Rep. 2021 Dec 15;11(1):24067. doi: 10.1038/s41598-021-02527-1.
Results Reference
derived

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A Study of CAN008 for Newly Diagnosed Glioblastoma Multiforme

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