Malignant Pleural EffusionsPhase 1NCT03869697
Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Pleural Effusions
A Phase 1 study testing SCB-313 in people with Malignant Pleural Effusions, run by Clover Biopharmaceuticals AUS Pty at 4 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Effusions
- What is being tested?
- SCB-313
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 4 sitesAustralia
- Study dates
- 20 Nov 2019to 23 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Liverpool Hospital
Liverpool, New South Wales, 2170
SCGH (Sir Charles Gairdner Hospital)
Nedlands, Western Australia, 6009
Orange Health Service
Orange, New South Wales, 2800
The Royal Melbourne Hospital
Parkville, Victoria, 3050
About this study
Official 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
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.
- Conditions
- Malignant Pleural Effusions
- Being tested
- SCB-313
- Medical subject headings
- Pleural Effusion, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SCB-313Drug
Also called recombinant human TRAIL-Trimer fusion protein
5 mg or 20 mg lyophilized powder in a single-use glass vial
| Study group | Role | What they receive |
|---|---|---|
| SCB-313 | Experimental | 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. Receives: Drug: SCB-313 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of DLT
Occurrence of dose limiting toxicity (DLT)
Measured: Up to 21 days after start of treatment
Secondary outcomes (33)
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
Measured: Up to 21 days after start of treatment
Immunogenicity
Occurrence of binding and neutralizing anti-SCB-313 antibodies
Measured: 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.
Measured: 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
Measured: 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.
- 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.
Measured: Up to 6 months after start of treatment
Blood oxygen levels
To compare blood oxygen levels during the study
Measured: Up to 21 days after start of treatment
Overall survival
The time from the first dose of SCB-313 until death from any cause.
Measured: Up to 6 months after start of treatment
Pharmacokinetics (Cmax)
Maximum SCB-313 concentration
Measured: Up to 4 days after start of treatment
Pharmacokinetics(Cmax/D)
Dose-normalized Cmax of SCB-313
Measured: Up to 4 days after start of treatment
Pharmacokinetics(Tmax)
Time to Cmax of SCB-313
Measured: 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
Measured: Up to 4 days after start of treatment
Pharmacokinetics (AUC0-24/D)
Dose-normalized AUC0-24
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 4 days after start of treatment
Pharmacokinetics (AUC 0-inf)
Area under the curve from time zero extrapolated to infinity
Measured: Up to 4 days after start of treatment
Pharmacokinetics (AUC0-inf/D)
Dose-normalized AUC0-inf
Measured: Up to 4 days after start of treatment
Pharmacokinetics (t1/2)
Terminal half-life
Measured: Up to 4 days after start of treatment
Pharmacokinetics (CL/F serum only)
Apparent systemic clearance after intrapleural dosing
Measured: Up to 4 days after start of treatment
Pharmacokinetics (Vz/F serum only)
Apparent volume of distribution after intrapleural dosing
Measured: Up to 4 days after start of treatment
Pharmacokinetics (λz)
Terminal rate constant
Measured: Up to 4 days after start of treatment
Tumor response
Tumor response in patients with measurable disease using RECIST v1.1 as applicable.
Measured: Up to 6 months after start of treatment
Carcinoembryonic antigen (CEA)
Changes in serum tumor markers
Measured: Up to 21 days after start of treatment
CA-125
Changes in serum tumor markers
Measured: Up to 21 days after start of treatment
CA-19-9
Changes in serum tumor markers
Measured: Up to 21 days after start of treatment
Changes in 24-hour urine volume
Measured urine volume at baseline and postdose
Measured: Up to 4 days after start of treatment
Changes in GFR
The changes in glomerular filtration rate
Measured: Up to 4 days after start of treatment
Changes in tumor cell count in pleural effusion samples
The changes in tumor cell count
Measured: Up to 4 days after start of treatment
Caspase-cleaved CK18
Changes in serum PD biomarker
Measured: Up to 10 days after start of treatment
KRAS mutation
Predictive biomarker analysis (assessed using archival tumor specimens )
Measured: Baseline
MMR defects
Predictive biomarker analysis (assessed using archival tumor specimens )
Measured: Baseline
Bcl2 overexpression
Predictive biomarker analysis (assessed using archival tumor specimens )
Measured: Baseline
TRAIL resistance
Predictive biomarker analysis (assessed using pleural effusion samples)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2019
- Study start20 Nov 2019
- Primary completion4 Nov 2021
- Study completion23 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural EffusionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clover Biopharmaceuticals AUS Pty
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03869697
- Sponsor's protocol ID
- CLO-SCB-313-002
- Status last verified
- Feb 2022
- First submitted
- 1 Mar 2019
- Last updated
- 2 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03869697
- Acronym / sponsor ID
- CLO-SCB-313-002
- Conditions
- Malignant Pleural Effusions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Clover Biopharmaceuticals AUS PtyIndustry (pharma, biotech, devices)
- Study start
- 20 Nov 2019 (actual)
- Primary completion
- 4 Nov 2021 (actual)
- Study completion
- 23 Nov 2021 (actual)
- First posted
- 11 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SCB-313 | Experimental | Drug: SCB-313Cohorts 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SCB-313Also: recombinant human TRAIL-Trimer fusion protein5 mg or 20 mg lyophilized powder in a single-use glass vial | Drug | SCB-313 |
Primary outcome
Occurrence of DLT
Time frame: Up to 21 days after start of treatment
Occurrence of dose limiting toxicity (DLT)
33 secondary outcomes
SAEs or TEAEs
Time frame: Up to 21 days after start of treatment
Immunogenicity
Time frame: Up to 21 days after start of treatment
Pleural effusion response rate at Day 21
Time frame: At Day 21 after start of treatment
Pleural effusion drainage-free rate 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.
Time frame: Up to 6 months after start of treatment
Blood oxygen levels
Time frame: Up to 21 days after start of treatment
Overall survival
Time frame: Up to 6 months after start of treatment
Pharmacokinetics (Cmax)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics(Cmax/D)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics(Tmax)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics ([AUC]0-24)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (AUC0-24/D)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics ((AUC0-last))
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (Ctrough)
Time frame: Up to 4 days after start of treatment
Amount of drug in pleural effusion
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (AUC 0-inf)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (AUC0-inf/D)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (t1/2)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (CL/F serum only)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (Vz/F serum only)
Time frame: Up to 4 days after start of treatment
Pharmacokinetics (λz)
Time frame: Up to 4 days after start of treatment
Tumor response
Time frame: Up to 6 months after start of treatment
Carcinoembryonic antigen (CEA)
Time frame: Up to 21 days after start of treatment
CA-125
Time frame: Up to 21 days after start of treatment
CA-19-9
Time frame: Up to 21 days after start of treatment
Changes in 24-hour urine volume
Time frame: Up to 4 days after start of treatment
Changes in GFR
Time frame: Up to 4 days after start of treatment
Changes in tumor cell count in pleural effusion samples
Time frame: Up to 4 days after start of treatment
Caspase-cleaved CK18
Time frame: Up to 10 days after start of treatment
KRAS mutation
Time frame: Baseline
MMR defects
Time frame: Baseline
Bcl2 overexpression
Time frame: Baseline
TRAIL resistance
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SCB-313 in people with Malignant Pleural Effusions, run by Clover Biopharmaceuticals AUS Pty at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of DLT (time frame: Up to 21 days after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2022.