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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03869697




Registration number
NCT03869697
Ethics application status
Date submitted
1/03/2019
Date registered
11/03/2019
Date last updated
5/02/2020

Titles & IDs
Public title
Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Pleural Effusions
Scientific title
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
Secondary ID [1] 0 0
CLO-SCB-313-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Effusions 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SCB-313

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.


Treatment: Drugs: SCB-313
5 mg or 20 mg lyophilized powder in a single-use glass vial

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of DLT - Occurrence of dose limiting toxicity (DLT)
Timepoint [1] 0 0
Up to 21 days after start of treatment
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to 21 days after start of treatment
Secondary outcome [2] 0 0
Immunogenicity - Occurrence of binding and neutralizing anti-SCB-313 antibodies
Timepoint [2] 0 0
Up to 21 days after start of treatment
Secondary outcome [3] 0 0
Pleural effusion response rate at Day 21 - Based on chest radiographs at Day 21, compared to Baseline.
Timepoint [3] 0 0
At Day 21 after start of treatment
Secondary outcome [4] 0 0
Pleural effusion drainage-free rate at Day 21 - Defined as the probability of being effusion-drainage free at Day 21
Timepoint [4] 0 0
At Day 21 after start of treatment
Secondary outcome [5] 0 0
The changes in effusion volume and flow rate after SCB-313 treatment , and at next drainage over the baseline daily effusion flow rate. - The baseline daily effusion flow rate will be measured.
Effusion flow rate will be calculated from the effusion volume drained over the time elapsed between drainages.
Effusion flow rate at next pleural drainage will be calculated from the volume over the time elapsed between drainages.
Timepoint [5] 0 0
Up to 6 months after start of treatment
Secondary outcome [6] 0 0
Blood oxygen levels - To compare blood oxygen levels during the study
Timepoint [6] 0 0
Up to 21 days after start of treatment
Secondary outcome [7] 0 0
Overall survival - The time from the first dose of SCB-313 until death from any cause.
Timepoint [7] 0 0
Up to 6 months after start of treatment
Secondary outcome [8] 0 0
Pharmacokinetics (Cmax) - Maximum SCB-313 concentration
Timepoint [8] 0 0
Up to 4 days after start of treatment
Secondary outcome [9] 0 0
Pharmacokinetics(Cmax/D) - Dose-normalized Cmax of SCB-313
Timepoint [9] 0 0
Up to 4 days after start of treatment
Secondary outcome [10] 0 0
Pharmacokinetics(Tmax) - Time to Cmax of SCB-313
Timepoint [10] 0 0
Up to 4 days after start of treatment
Secondary outcome [11] 0 0
Pharmacokinetics ([AUC]0-24) - Area under SCB-313 concentration time curve from zero to 24 hours after dosing
Timepoint [11] 0 0
Up to 4 days after start of treatment
Secondary outcome [12] 0 0
Pharmacokinetics (AUC0-24/D) - Dose-normalized AUC0-24
Timepoint [12] 0 0
Up to 4 days after start of treatment
Secondary outcome [13] 0 0
Pharmacokinetics ((AUC0-last)) - Area under the SCB-313 concentration-time curve from time zero to the last quantifiable concentration time point
Timepoint [13] 0 0
Up to 4 days after start of treatment
Secondary outcome [14] 0 0
Pharmacokinetics (Ctrough) - Trough concentration (Ctrough) at each predose time point and at 24 hours after the last dose
Timepoint [14] 0 0
Up to 4 days after start of treatment
Secondary outcome [15] 0 0
Amount of drug in pleural effusion - Amount of SCB-313 in pleural effusion at 24 hours after each dose
Timepoint [15] 0 0
Up to 4 days after start of treatment
Secondary outcome [16] 0 0
Pharmacokinetics (AUC 0-inf) - Area under the curve from time zero extrapolated to infinity
Timepoint [16] 0 0
Up to 4 days after start of treatment
Secondary outcome [17] 0 0
Pharmacokinetics (AUC0-inf/D) - Dose-normalized AUC0-inf
Timepoint [17] 0 0
Up to 4 days after start of treatment
Secondary outcome [18] 0 0
Pharmacokinetics (t1/2) - Terminal half-life
Timepoint [18] 0 0
Up to 4 days after start of treatment
Secondary outcome [19] 0 0
Pharmacokinetics (CL/F serum only) - Apparent systemic clearance after intrapleural dosing
Timepoint [19] 0 0
Up to 4 days after start of treatment
Secondary outcome [20] 0 0
Pharmacokinetics (Vz/F serum only) - Apparent volume of distribution after intrapleural dosing
Timepoint [20] 0 0
Up to 4 days after start of treatment
Secondary outcome [21] 0 0
Pharmacokinetics (?z) - Terminal rate constant
Timepoint [21] 0 0
Up to 4 days after start of treatment
Secondary outcome [22] 0 0
Tumor response - Tumor response in patients with measurable disease using RECIST v1.1 as applicable.
Timepoint [22] 0 0
Up to 6 months after start of treatment
Secondary outcome [23] 0 0
Carcinoembryonic antigen (CEA) - Changes in serum tumor markers
Timepoint [23] 0 0
Up to 21 days after start of treatment
Secondary outcome [24] 0 0
CA-125 - Changes in serum tumor markers
Timepoint [24] 0 0
Up to 21 days after start of treatment
Secondary outcome [25] 0 0
CA-19-9 - Changes in serum tumor markers
Timepoint [25] 0 0
Up to 21 days after start of treatment
Secondary outcome [26] 0 0
Changes in 24-hour urine volume - Measured urine volume at baseline and postdose
Timepoint [26] 0 0
Up to 4 days after start of treatment
Secondary outcome [27] 0 0
Changes in GFR - The changes in glomerular filtration rate
Timepoint [27] 0 0
Up to 4 days after start of treatment
Secondary outcome [28] 0 0
Changes in tumor cell count in pleural effusion samples - The changes in tumor cell count
Timepoint [28] 0 0
Up to 4 days after start of treatment
Secondary outcome [29] 0 0
Caspase-cleaved CK18 - Changes in serum PD biomarker
Timepoint [29] 0 0
Up to 10 days after start of treatment
Secondary outcome [30] 0 0
KRAS mutation - Predictive biomarker analysis (assessed using archival tumor specimens )
Timepoint [30] 0 0
Baseline
Secondary outcome [31] 0 0
MMR defects - Predictive biomarker analysis (assessed using archival tumor specimens )
Timepoint [31] 0 0
Baseline
Secondary outcome [32] 0 0
Bcl2 overexpression - Predictive biomarker analysis (assessed using archival tumor specimens )
Timepoint [32] 0 0
Baseline
Secondary outcome [33] 0 0
TRAIL resistance - Predictive biomarker analysis (assessed using pleural effusion samples)
Timepoint [33] 0 0
Baseline

Eligibility
Key inclusion criteria
1. Histologically or cytologically confirmed cancer of any primary tumor type.

2. 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.

3. 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.

4. Life expectancy of at least 8 weeks.

5. Age =18 years.

6. Adequate hematologic function, defined as:

1. Platelet count =75,000/µL;

2. Prothrombin time and activated partial thromboplastin time =1.5 times the upper
limit of normal (ULN);

3. Absolute neutrophil count =1,500 µL;

4. 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).

7. Adequate renal function, defined as creatinine clearance >40 mL/minute.

8. Adequate liver function, defined as:

1. Aspartate aminotransferase and alanine aminotransferase =2.0 times ULN;

2. Bilirubin =2.0 times ULN, unless patient has known Gilbert's syndrome.

9. 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.

10. Willing to attend follow-up visits on Days 10, and 21 after the first study drug
administration.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significantly loculated pleural effusions not amenable to drainage or patient is
unlikely to benefit from intrapleural therapy.

2. Concurrent use of any investigational product (IP) or investigational medicine within
28 days before Day 1 of study drug administration.

3. 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).

4. 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.

5. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous
antibiotics within 2 weeks prior to enrollment.

6. Clinical unstable or uncontrolled concomitant hematologic, cardiovascular, pulmonary,
hepatic, renal, pancreatic, or endocrine diseases.

7. History of gross hemoptysis (>2.5 mL).

8. Residual adverse events (AEs) > Grade 2 from previous treatment.

9. Evidence or suspicion of relevant psychiatric impairment, including alcohol or
recreational drug abuse.

10. 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.

11. 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).

12. Major surgery (open procedures) within 4 weeks prior to enrollment.

13. Patient with ileus within 30 days prior to Screening.

14. Positive serology test for human immunodeficiency virus type 1 and/or 2, or known
history of other immunodeficiency disease.

15. Live vaccine within 2 weeks prior to enrollment.

16. Scheduled participation in another clinical study involving an investigational product
or device during the DLT observation period of this study.

17. Previous treatment with a TRAIL-based therapy or death receptor 4/5 agonist therapy.

18. Known or suspected hypersensitivity to any component of SCB-313.

19. Any further condition which, in the opinion of the Investigator, may result in undue
risk of the patient by participating in the present study.

20. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord
compression.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Orange Health Service - Orange
Recruitment hospital [3] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [4] 0 0
SCGH (Sir Charles Gairdner Hospital) - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Clover Biopharmaceuticals AUS Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03869697
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gary Hammerschlag
Address 0 0
Country 0 0
Phone 0 0
61393427708
Fax 0 0
Email 0 0
Gary.Hammerschlag@mh.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03869697