A Study of CAN008 for Newly Diagnosed Glioblastoma Multiforme

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase I Study of CAN008 Plus Concomitant Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02853565
• Other study ID #: CAN-B1-008-L-002
• Status: Completed
• Phase: Phase 1
• Start date: August 2016
• Est. completion date: September 2018

Study information

• Verified date: September 2017
• Source: CANbridge Life Sciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. To describe the toxicity associated with this regimen in adult patients with newly diagnosed glioblastoma multiforme.

2. To determine the duration of disease free survival and overall survival associated with this therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• CAN008
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)

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital, Linkou	Taipei
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
CANbridge Life Sciences Ltd.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	PK profile measured by CAN008 serum concentrations	CAN008 serum concentrations will be determined.	up to 2 years
Secondary	PK profile measured by Maximum Plasma Concentration [Cmax]	Maximum Plasma Concentration [Cmax] will be determined.	up to 2 years
Secondary	PK profile measured by Area Under the Curve [AUC]	Area Under the Curve [AUC] will be determined.	up to 2 years
Secondary	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.	up to 2 years
Secondary	Preliminary efficacy (Overall Survival [OS])	Overall survival (OS) is defined as the time from the first dose of CAN008 to death.	up to 2 years