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Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Pleural Effusions

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ClinicalTrials.gov Identifier: NCT03869697
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
Clover Biopharmaceuticals AUS Pty Ltd

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.

Condition or disease Intervention/treatment Phase
Malignant Pleural Effusions Drug: SCB-313 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 17, 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Arm Intervention/treatment
Experimental: SCB-313 Drug: SCB-313
1 intrapleural injections of SCB-313 on Day 1 for the SAD cohort, and 3 intrapleural injections of SCB-313 on Days 1, 2 and 3 for the MAD cohort.
Other Name: recombinant human TRAIL-Trimer fusion protein




Primary Outcome Measures :
  1. Occurrence of DLT [ Time Frame: Up to 30 days after start of treatment ]
    Occurrence of dose limiting toxicity (DLT)


Secondary Outcome Measures :
  1. SAEs or TEAEs [ Time Frame: Up to 30 days after start of treatment ]
    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

  2. Immunogenicity [ Time Frame: Up to 30 days after start of treatment ]
    Occurrence of binding and neutralizing anti-SCB-313 antibodies

  3. Pleural effusion response rate at Day 30 [ Time Frame: At Day 30 after start of treatment ]
    Based on chest radiographs at Day 30, compared to Baseline.

  4. Pleural effusion drainage-free rate at Day 30 [ Time Frame: At Day 30 after start of treatment ]
    Defined as the probability of being effusion-drainage free at Day 30

  5. 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 ]
    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.

  6. Blood oxygen levels [ Time Frame: Up to 30 days after start of treatment ]
    To compare blood oxygen levels during the study

  7. Overall survival [ Time Frame: Up to 6 months after start of treatment ]
    The time from the first dose of SCB-313 until death from any cause.

  8. Pharmacokinetics (Cmax) [ Time Frame: Up to 4 days after start of treatment ]
    Maximum SCB-313 concentration

  9. Pharmacokinetics(Cmax/D) [ Time Frame: Up to 4 days after start of treatment ]
    Dose-normalized Cmax of SCB-313

  10. Pharmacokinetics(Tmax) [ Time Frame: Up to 4 days after start of treatment ]
    Time to Cmax of SCB-313

  11. Pharmacokinetics ([AUC]0-24) [ Time Frame: Up to 4 days after start of treatment ]
    Area under SCB-313 concentration time curve from zero to 24 hours after dosing

  12. Pharmacokinetics (AUC0-24/D) [ Time Frame: Up to 4 days after start of treatment ]
    Dose-normalized AUC0-24

  13. Pharmacokinetics ((AUC0-last)) [ Time Frame: Up to 4 days after start of treatment ]
    Area under the SCB-313 concentration-time curve from time zero to the last quantifiable concentration time point

  14. Pharmacokinetics (Ctrough) [ Time Frame: Up to 4 days after start of treatment ]
    Trough concentration (Ctrough) at each predose time point and at 24 hours after the last dose

  15. Amount of drug in pleural effusion [ Time Frame: Up to 4 days after start of treatment ]
    Amount of SCB-313 in pleural effusion at 24 hours after each dose

  16. Pharmacokinetics (AUC 0-inf) [ Time Frame: Up to 4 days after start of treatment ]
    Area under the curve from time zero extrapolated to infinity

  17. Pharmacokinetics (AUC0-inf/D) [ Time Frame: Up to 4 days after start of treatment ]
    Dose-normalized AUC0-inf

  18. Pharmacokinetics (t1/2) [ Time Frame: Up to 4 days after start of treatment ]
    Terminal half-life

  19. Pharmacokinetics (CL/F serum only) [ Time Frame: Up to 4 days after start of treatment ]
    Apparent systemic clearance after intrapleural dosing

  20. Pharmacokinetics (Vz/F serum only) [ Time Frame: Up to 4 days after start of treatment ]
    Apparent volume of distribution after intrapleural dosing

  21. Pharmacokinetics (λz) [ Time Frame: Up to 4 days after start of treatment ]
    Terminal rate constant

  22. Tumor response [ Time Frame: Up to 6 months after start of treatment ]
    Tumor response in patients with measurable disease using RECIST v1.1 as applicable.

  23. Carcinoembryonic antigen (CEA) [ Time Frame: Up to 30 days after start of treatment ]
    Changes in serum tumor markers

  24. CA-125 [ Time Frame: Up to 30 days after start of treatment ]
    Changes in serum tumor markers

  25. CA-19-9 [ Time Frame: Up to 30 days after start of treatment ]
    Changes in serum tumor markers

  26. Changes in 24-hour urine volume [ Time Frame: Up to 4 days after start of treatment ]
    Measured urine volume at baseline and postdose

  27. Changes in GFR [ Time Frame: Up to 4 days after start of treatment ]
    The changes in glomerular filtration rate

  28. Changes in tumor cell count in pleural effusion samples [ Time Frame: Up to 4 days after start of treatment ]
    The changes in tumor cell count

  29. Caspase-cleaved CK18 [ Time Frame: Up to 10 days after start of treatment ]
    Changes in serum PD biomarker

  30. KRAS mutation [ Time Frame: Baseline ]
    Predictive biomarker analysis (assessed using archival tumor specimens )

  31. MMR defects [ Time Frame: Baseline ]
    Predictive biomarker analysis (assessed using archival tumor specimens )

  32. Bcl2 overexpression [ Time Frame: Baseline ]
    Predictive biomarker analysis (assessed using archival tumor specimens )

  33. TRAIL resistance [ Time Frame: Baseline ]
    Predictive biomarker analysis (assessed using pleural effusion samples)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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. Body weight ≥45 kg and body mass index ≥17 kg/m2.
  7. Adequate hematologic function, defined as:

    1. Platelet count ≥100,000/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).
  8. Adequate renal function, defined as serum creatinine ≤2.0 times ULN and creatinine clearance >50 mL/minute.
  9. 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.
  10. 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.

  11. Willing to attend follow-up visits on Days 10, 20, and 30 after the first study drug administration.

Exclusion Criteria:

  1. Significantly loculated pleural effusions not amenable to drainage and patient is unlikely to benefit from intrapleural therapy.
  2. Bilateral pleural effusions.
  3. Prior antitumor therapy (chemotherapy) within 2 weeks, or small-molecule targeted therapy within 5 half-lives prior to enrollment, radiotherapy outside the chest field within 2 weeks, or radiotherapy inside the chest field within 12 weeks prior to enrollment. Prior therapy with monoclonal antibody should be stopped per Investigator's judgement making sure delayed side effects will not interfere with the DLT evaluation period after SCB-313 therapy.
  4. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous antibiotics within 2 weeks prior to enrollment.
  5. Symptoms or signs (including laboratory tests) of clinically significant concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
  6. History of gross hemoptysis (>2.5 mL).
  7. Residual adverse events (AEs) > Grade 2 from previous treatment.
  8. Evidence or suspicion of relevant psychiatric impairment, including alcohol or recreational drug abuse.
  9. 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 >450 msec at Baseline.
  10. 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).
  11. Left ventricular ejection fraction <40% as determined by echocardiography or multigated acquisition (MUGA) scan performed at Screening or within 90 days prior to enrollment.
  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 course 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03869697


Contacts
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Contact: Gary Hammerschlag 61393427708 Gary.Hammerschlag@mh.org.au

Locations
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Australia, New South Wales
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Jennifer Aung    (02) 8738 9163    Aflah.Roohullah@health.nsw.gov.au   
Principal Investigator: Aflah Roohullah         
Australia, Victoria
The Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Contact: Sue Schulz    03 9342 8490    susanne.schulz@mh.org.au   
Principal Investigator: Gary Hammerschlag         
Australia, Western Australia
SCGH (Sir Charles Gairdner Hospital) Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Cathy Read    +61 (8) 6457 1754    Cathy.Read@health.wa.gov.au   
Principal Investigator: Gary Lee         
Sponsors and Collaborators
Clover Biopharmaceuticals AUS Pty Ltd

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Responsible Party: Clover Biopharmaceuticals AUS Pty Ltd
ClinicalTrials.gov Identifier: NCT03869697     History of Changes
Other Study ID Numbers: CLO-SCB-313-002
First Posted: March 11, 2019    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Pleural Effusion
Pleural Effusion, Malignant
Pleural Diseases
Respiratory Tract Diseases
Pleural Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms