- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03869697
Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Pleural Effusions
A Phase I Study Evaluating the Safety, Tolerability, Efficacy, and Pharmacokinetics of SCB-313, a Fully-Human TRAIL-Trimer Fusion Protein, for the Treatment of Malignant Pleural Effusions
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New South Wales
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Liverpool, New South Wales, Australia, 2170
- Liverpool Hospital
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Orange, New South Wales, Australia, 2800
- Orange Health Service
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Victoria
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Parkville, Victoria, Australia, 3050
- The Royal Melbourne Hospital
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- SCGH (Sir Charles Gairdner Hospital)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed cancer of any primary tumor type.
- Malignant pleural effusion causing respiratory symptoms requiring drainage that is histologically or cytologically confirmed; or pleural effusion with radiologically proven pleural malignancy as diagnosed in normal clinical practice on thoracic computed tomography in the absence of histocytological or cytological proof.
- Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2. Patients with an ECOG performance status of 3 may be included if the Investigator determines that removal of pleural fluid would improve their performance status to 2 or better.
- Life expectancy of at least 8 weeks.
- Age ≥18 years.
Adequate hematologic function, defined as:
- Platelet count ≥75,000/μL;
- Prothrombin time and activated partial thromboplastin time ≤1.5 times the upper limit of normal (ULN);
- Absolute neutrophil count ≥1,500 μL;
- Hemoglobin ≥8 g/dL (transfusion and erythropoietic agents are allowed). In case there is existence of active bleeding or other persistent condition of either increased destruction or impaired production of erythrocytes, which may require repeated transfusion or erythropoietic treatment, the eligibility must be discussed with the Sponsor on a case-by-case basis prior to randomization).
- Adequate renal function, defined as creatinine clearance >40 mL/minute.
Adequate liver function, defined as:
- Aspartate aminotransferase and alanine aminotransferase ≤2.0 times ULN;
- Bilirubin ≤2.0 times ULN, unless patient has known Gilbert's syndrome.
Female patients of childbearing potential (excluding women who have undergone surgical sterilization or are menopausal, defined as no menstrual periods for 1 year or more without any other medical reasons) are eligible if they have negative serum pregnancy test result 7 days before the first dose of SCB-313 and are willing to use an effective method of birth control/contraception to prevent pregnancy until 6 months after discontinuation of SCB-313.
Both men and women of reproductive potential must agree to use effective contraception during the study and for 6 months after discontinuation of SCB-313.
Note: Contraceptive methods that are considered highly effective areas follows: total abstinence, intrauterine device, double barrier method (such as condom plus diaphragm with spermicide), contraceptive implant, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release), or vasectomized partner with confirmed azoospermia.
- Willing to attend follow-up visits on Days 10, and 21 after the first study drug administration.
Exclusion Criteria:
- Significantly loculated pleural effusions not amenable to drainage or patient is unlikely to benefit from intrapleural therapy.
- Concurrent use of any investigational product (IP) or investigational medicine within 28 days before Day 1 of study drug administration.
- Radiotherapy outside the chest field within 2 weeks, or radical radiotherapy to pleural or lung lesions within 8 weeks prior to enrollment (Note: palliative radiotherapy to the chest is allowed).
- Start a new systemic anticancer therapy, including chemotherapy, targeted therapy, immuno-oncology (I-O) therapy regimen, within 28 days before Day 1 of study drug administration or during DLT observation period.
- Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous antibiotics within 2 weeks prior to enrollment.
- Clinical unstable or uncontrolled concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
- History of gross hemoptysis (>2.5 mL).
- Residual adverse events (AEs) > Grade 2 from previous treatment.
- Evidence or suspicion of relevant psychiatric impairment, including alcohol or recreational drug abuse.
- Myocardial infarction within 6 months prior to treatment and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication, and/or long QT syndrome or QT/QTc interval >480 msec at Baseline.
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures (note: no more than 3 repeated measures allowed).
- Major surgery (open procedures) within 4 weeks prior to enrollment.
- Patient with ileus within 30 days prior to Screening.
- Positive serology test for human immunodeficiency virus type 1 and/or 2, or known history of other immunodeficiency disease.
- Live vaccine within 2 weeks prior to enrollment.
- Scheduled participation in another clinical study involving an investigational product or device during the DLT observation period of this study.
- Previous treatment with a TRAIL-based therapy or death receptor 4/5 agonist therapy.
- Known or suspected hypersensitivity to any component of SCB-313.
- Any further condition which, in the opinion of the Investigator, may result in undue risk of the patient by participating in the present study.
- Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: SCB-313
Cohorts in SAD phase: 5 mg, 10mg, 20mg, 40mg, 80 mg.
Cohort in MAD phase: biological effective dose determined from SAD phase. 1 intrapleural injection of SCB-313 on Day 1 for the SAD cohorts, and 3 intrapleural injections of SCB-313 on Days 1, 2 and 3 for the MAD cohort.
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5 mg or 20 mg lyophilized powder in a single-use glass vial
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Occurrence of DLT
Time Frame: Up to 21 days after start of treatment
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Occurrence of dose limiting toxicity (DLT)
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Up to 21 days after start of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SAEs or TEAEs
Time Frame: Up to 21 days after start of treatment
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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
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Up to 21 days after start of treatment
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Immunogenicity
Time Frame: Up to 21 days after start of treatment
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Occurrence of binding and neutralizing anti-SCB-313 antibodies
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Up to 21 days after start of treatment
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Pleural effusion response rate at Day 21
Time Frame: At Day 21 after start of treatment
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Based on chest radiographs at Day 21, compared to Baseline.
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At Day 21 after start of treatment
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Pleural effusion drainage-free rate at Day 21
Time Frame: At Day 21 after start of treatment
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Defined as the probability of being effusion-drainage free at Day 21
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At Day 21 after start of treatment
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The changes in effusion volume and flow rate after SCB-313 treatment , and at next drainage over the baseline daily effusion flow rate.
Time Frame: Up to 6 months after start of treatment
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Up to 6 months after start of treatment
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Blood oxygen levels
Time Frame: Up to 21 days after start of treatment
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To compare blood oxygen levels during the study
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Up to 21 days after start of treatment
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Overall survival
Time Frame: Up to 6 months after start of treatment
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The time from the first dose of SCB-313 until death from any cause.
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Up to 6 months after start of treatment
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Pharmacokinetics (Cmax)
Time Frame: Up to 4 days after start of treatment
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Maximum SCB-313 concentration
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Up to 4 days after start of treatment
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Pharmacokinetics(Cmax/D)
Time Frame: Up to 4 days after start of treatment
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Dose-normalized Cmax of SCB-313
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Up to 4 days after start of treatment
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Pharmacokinetics(Tmax)
Time Frame: Up to 4 days after start of treatment
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Time to Cmax of SCB-313
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Up to 4 days after start of treatment
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Pharmacokinetics ([AUC]0-24)
Time Frame: Up to 4 days after start of treatment
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Area under SCB-313 concentration time curve from zero to 24 hours after dosing
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Up to 4 days after start of treatment
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Pharmacokinetics (AUC0-24/D)
Time Frame: Up to 4 days after start of treatment
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Dose-normalized AUC0-24
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Up to 4 days after start of treatment
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Pharmacokinetics ((AUC0-last))
Time Frame: Up to 4 days after start of treatment
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Area under the SCB-313 concentration-time curve from time zero to the last quantifiable concentration time point
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Up to 4 days after start of treatment
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Pharmacokinetics (Ctrough)
Time Frame: Up to 4 days after start of treatment
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Trough concentration (Ctrough) at each predose time point and at 24 hours after the last dose
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Up to 4 days after start of treatment
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Amount of drug in pleural effusion
Time Frame: Up to 4 days after start of treatment
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Amount of SCB-313 in pleural effusion at 24 hours after each dose
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Up to 4 days after start of treatment
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Pharmacokinetics (AUC 0-inf)
Time Frame: Up to 4 days after start of treatment
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Area under the curve from time zero extrapolated to infinity
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Up to 4 days after start of treatment
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Pharmacokinetics (AUC0-inf/D)
Time Frame: Up to 4 days after start of treatment
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Dose-normalized AUC0-inf
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Up to 4 days after start of treatment
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Pharmacokinetics (t1/2)
Time Frame: Up to 4 days after start of treatment
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Terminal half-life
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Up to 4 days after start of treatment
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Pharmacokinetics (CL/F serum only)
Time Frame: Up to 4 days after start of treatment
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Apparent systemic clearance after intrapleural dosing
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Up to 4 days after start of treatment
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Pharmacokinetics (Vz/F serum only)
Time Frame: Up to 4 days after start of treatment
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Apparent volume of distribution after intrapleural dosing
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Up to 4 days after start of treatment
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Pharmacokinetics (λz)
Time Frame: Up to 4 days after start of treatment
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Terminal rate constant
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Up to 4 days after start of treatment
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Tumor response
Time Frame: Up to 6 months after start of treatment
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Tumor response in patients with measurable disease using RECIST v1.1 as applicable.
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Up to 6 months after start of treatment
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Carcinoembryonic antigen (CEA)
Time Frame: Up to 21 days after start of treatment
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Changes in serum tumor markers
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Up to 21 days after start of treatment
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CA-125
Time Frame: Up to 21 days after start of treatment
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Changes in serum tumor markers
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Up to 21 days after start of treatment
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CA-19-9
Time Frame: Up to 21 days after start of treatment
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Changes in serum tumor markers
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Up to 21 days after start of treatment
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Changes in 24-hour urine volume
Time Frame: Up to 4 days after start of treatment
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Measured urine volume at baseline and postdose
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Up to 4 days after start of treatment
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Changes in GFR
Time Frame: Up to 4 days after start of treatment
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The changes in glomerular filtration rate
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Up to 4 days after start of treatment
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Changes in tumor cell count in pleural effusion samples
Time Frame: Up to 4 days after start of treatment
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The changes in tumor cell count
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Up to 4 days after start of treatment
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Caspase-cleaved CK18
Time Frame: Up to 10 days after start of treatment
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Changes in serum PD biomarker
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Up to 10 days after start of treatment
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KRAS mutation
Time Frame: Baseline
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Predictive biomarker analysis (assessed using archival tumor specimens )
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Baseline
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MMR defects
Time Frame: Baseline
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Predictive biomarker analysis (assessed using archival tumor specimens )
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Baseline
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Bcl2 overexpression
Time Frame: Baseline
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Predictive biomarker analysis (assessed using archival tumor specimens )
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Baseline
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TRAIL resistance
Time Frame: Baseline
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Predictive biomarker analysis (assessed using pleural effusion samples)
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Baseline
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLO-SCB-313-002
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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