The purpose of this study is to evaluate the safety, tolerability, preliminary efficacy, and PK/PD of SCB-313 (recombinant human TRAIL-Trimer fusion protein) administered once via intrapleural injection (SAD) and once daily over 2 to 3 days (MAD)for the treatment of cancer patients with symptomatic malignant pleural effusions requiring drainage.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
5 mg or 20 mg lyophilized powder in a single-use glass vial
Liverpool Hospital
Liverpool, New South Wales, Australia
Orange Health Service
Orange, New South Wales, Australia
The Royal Melbourne Hospital
Parkville, Victoria, Australia
SCGH (Sir Charles Gairdner Hospital)
Nedlands, Western Australia, Australia
Occurrence of DLT
Occurrence of dose limiting toxicity (DLT)
Time frame: Up to 21 days after start of treatment
SAEs or TEAEs
Occurrence of serious adverse events (SAEs) and/or treatment-emergent adverse events (TEAEs) regardless of causality or relationship to SCB-313, graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
Time frame: Up to 21 days after start of treatment
Immunogenicity
Occurrence of binding and neutralizing anti-SCB-313 antibodies
Time frame: Up to 21 days after start of treatment
Pleural effusion response rate at Day 21
Based on chest radiographs at Day 21, compared to Baseline.
Time frame: At Day 21 after start of treatment
Pleural effusion drainage-free rate at Day 21
Defined as the probability of being effusion-drainage free at Day 21
Time frame: At Day 21 after start of treatment
The changes in effusion volume and flow rate after SCB-313 treatment , and at next drainage over the baseline daily effusion flow rate.
1. The baseline daily effusion flow rate will be measured. 2. Effusion flow rate will be calculated from the effusion volume drained over the time elapsed between drainages. 3. Effusion flow rate at next pleural drainage will be calculated from the volume over the time elapsed between drainages.
Time frame: Up to 6 months after start of treatment
Blood oxygen levels
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To compare blood oxygen levels during the study
Time frame: Up to 21 days after start of treatment
Overall survival
The time from the first dose of SCB-313 until death from any cause.
Time frame: Up to 6 months after start of treatment
Pharmacokinetics (Cmax)
Maximum SCB-313 concentration
Time frame: Up to 4 days after start of treatment
Pharmacokinetics(Cmax/D)
Dose-normalized Cmax of SCB-313
Time frame: Up to 4 days after start of treatment
Pharmacokinetics(Tmax)
Time to Cmax of SCB-313
Time frame: Up to 4 days after start of treatment
Pharmacokinetics ([AUC]0-24)
Area under SCB-313 concentration time curve from zero to 24 hours after dosing
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (AUC0-24/D)
Dose-normalized AUC0-24
Time frame: Up to 4 days after start of treatment
Pharmacokinetics ((AUC0-last))
Area under the SCB-313 concentration-time curve from time zero to the last quantifiable concentration time point
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (Ctrough)
Trough concentration (Ctrough) at each predose time point and at 24 hours after the last dose
Time frame: Up to 4 days after start of treatment
Amount of drug in pleural effusion
Amount of SCB-313 in pleural effusion at 24 hours after each dose
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (AUC 0-inf)
Area under the curve from time zero extrapolated to infinity
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (AUC0-inf/D)
Dose-normalized AUC0-inf
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (t1/2)
Terminal half-life
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (CL/F serum only)
Apparent systemic clearance after intrapleural dosing
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (Vz/F serum only)
Apparent volume of distribution after intrapleural dosing
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (λz)
Terminal rate constant
Time frame: Up to 4 days after start of treatment
Tumor response
Tumor response in patients with measurable disease using RECIST v1.1 as applicable.
Time frame: Up to 6 months after start of treatment
Carcinoembryonic antigen (CEA)
Changes in serum tumor markers
Time frame: Up to 21 days after start of treatment
CA-125
Changes in serum tumor markers
Time frame: Up to 21 days after start of treatment
CA-19-9
Changes in serum tumor markers
Time frame: Up to 21 days after start of treatment
Changes in 24-hour urine volume
Measured urine volume at baseline and postdose
Time frame: Up to 4 days after start of treatment
Changes in GFR
The changes in glomerular filtration rate
Time frame: Up to 4 days after start of treatment
Changes in tumor cell count in pleural effusion samples
The changes in tumor cell count
Time frame: Up to 4 days after start of treatment
Caspase-cleaved CK18
Changes in serum PD biomarker
Time frame: Up to 10 days after start of treatment
KRAS mutation
Predictive biomarker analysis (assessed using archival tumor specimens )
Time frame: Baseline
MMR defects
Predictive biomarker analysis (assessed using archival tumor specimens )
Time frame: Baseline
Bcl2 overexpression
Predictive biomarker analysis (assessed using archival tumor specimens )
Time frame: Baseline
TRAIL resistance
Predictive biomarker analysis (assessed using pleural effusion samples)
Time frame: Baseline