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Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Peritoneal Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03443674
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Clover Biopharmaceuticals AUS Pty Ltd

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, immunogenicity, and PK/PD of SCB-313 (recombinant human TRAIL-Trimer fusion protein) administered twice weekly for 2 weeks via IP bolus injection for the treatment of patients with peritoneal malignancies, including but not limited to peritoneal carcinomatosis, malignant ascites, pseudomyxoma peritonei, and peritoneal mesothelioma.

Condition or disease Intervention/treatment Phase
Peritoneal Malignancies Drug: SCB-313 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Evaluating Safety, Tolerability, and Pharmacokinetics of SCB-313, a Fully-Human TRAIL-Trimer Fusion Protein, for the Treatment of Peritoneal Malignancies
Actual Study Start Date : June 18, 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: SCB-313
Dose escalation cohorts——10mg, 20mg, 40mg, 80mg, 160mg. For each cohort: administered twice weekly (eg.. Monday and Thursday or Tuesday and Friday) for 2 weeks (Days 1, 4, 8, and 11) by IP bolus injection.
Drug: SCB-313
Lyophilized powder in a single-use vial
Other Name: recombinant human TRAIL-Trimer fusion protein




Primary Outcome Measures :
  1. Safety and Tolerability: Occurrence of serious adverse events (SAEs) and/or TEAEs [ Time Frame: Up to 41 days after start of treatment ]
    Regardless of causality or relationship to SCB-313 graded using National Cancer Institute Common Terminology Criteria for Adverse Events Version.4.03 (NCI CTCAE v4.03).


Secondary Outcome Measures :
  1. Immunogenicity: Occurrence of binding and neutralizing anti-SCB-313 antibodies [ Time Frame: Up to 41 days after start of treatment ]
    Occurrence of binding and neutralizing anti-SCB-313 antibodies

  2. Pharmacokinetics (Cmax) [ Time Frame: Up to 12 days after start of treatment ]
    Maximum serum concentration

  3. Pharmacokinetics (Cmax/D) [ Time Frame: Up to 12 days after start of treatment ]
    Dose-normalized Cmax of SCB-313

  4. Pharmacokinetics (tmax) [ Time Frame: Up to 12 days after start of treatment ]
    Time to Cmax of SCB-313

  5. Pharmacokinetics ([AUC]0-24) [ Time Frame: Up to 12 days after start of treatment ]
    Area under SCB-313 concentration time curve from zero to 24 hours

  6. Pharmacokinetics (AUC0-24/D) [ Time Frame: Up to 12 days after start of treatment ]
    Dose-normalized AUC0-24 of SCB-313

  7. Pharmacokinetics ((AUC0-last)) [ Time Frame: Up to 12 days after start of treatment ]
    Area under curve from time 0 on Day 1 to the last quantifiable concentration time point

  8. Pharmacokinetics (Ctrough) [ Time Frame: Up to 12 days after start of treatment ]
    Trough concentration of SCB-313 at each predose and at 24 hours after the last dose


Other Outcome Measures:
  1. CEA [ Time Frame: Up to 6 months after start of treatment ]
    Changes in serum tumor marker(CEA)

  2. Caspase-cleaved cytokeratin 18 (CK-18) [ Time Frame: Up to 21 days after start of treatment ]
    Changes in serum PD biomarkers



Information from the National Library of Medicine

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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 peritoneal malignancies after failure or refusal of all approved therapies, and no better option available in the Investigator's opinion.
  2. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2 (Patients with ECOG score of 3 might be allowed to enter this trial per Investigator's judgment)
  3. Life expectancy of at least 8 weeks
  4. Age ≥18 years
  5. Body mass index ≥17.0 kg/m2
  6. Adequate hematological 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 serum creatinine ≤2.0 times ULN and creatinine clearance >45 mL/minute
  8. Adequate liver function, defined as:

    1. Aspartate aminotransferase and alanine aminotransferase ≤3 times ULN for patients without liver metastases, or ≤5 times ULN in the presence of liver metastases
    2. Bilirubin ≤1.5 times ULN, unless patient has known Gilbert's syndrome
  9. Female patients of childbearing potential (excluding women who have undergone surgical sterilization or menopause. Menopause is defined as the status where no menstrual periods continue for 1 year or more without any other medical reasons), are eligible if they have negative serum pregnancy testing within 7 days prior to first dosing and are willing to use an effective method of birth control/contraception to prevent pregnancy until 6 months after discontinuation of the 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 the SCB-313.

Note: Contraceptive methods that are considered highly effective are, for example, total abstinence, an intrauterine device, a double barrier method (such as condom plus diaphragm with spermicide), a contraceptive implant, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release), or have a vasectomized partner with confirmed azoospermia.

Exclusion Criteria:

  1. Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous (IV) antibiotics within 2 weeks prior to enrollment.
  2. Symptoms or signs (including laboratory tests) of clinically significant concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
  3. Residual adverse events (AEs) > Grade 2 from previous treatment.
  4. Evidence or suspicion of relevant psychiatric impairment including alcohol or recreational drug abuse.
  5. 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.
  6. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures.
  7. Left ventricular ejection fraction <40% as determined by echocardiography performed at screening or within 90 days prior to enrollment.
  8. Prior anti-tumor therapy (chemotherapy) within 2 weeks, hormone therapy or palliative extra-abdominal radiotherapy within at least 1 week, or small-molecule targeted therapy within 5 half-lives prior to enrollment. Prior therapy with monoclonal antibody should be stopped after Investigator's judgement making sure delayed side effects will not interfere with the dose limiting toxicity (DLT) evaluation period after SCB-313 therapy.
  9. Major surgery within 4 weeks prior to enrollment.
  10. Patient with ileus within 30 days prior to screening.
  11. Positive serology test for human immunodeficiency virus Type 1 and 2 or known history of other immunodeficiency disease.
  12. Live vaccine within 2 weeks prior to enrollment.
  13. Scheduled participation in another clinical study involving an investigational product or device during the course of this study.
  14. Previous treatment with a TRAIL-based therapy or death receptor (DR) 4/5 agonist therapy.
  15. Known or suspected hypersensitivity to any component of the SCB-313.
  16. Any further condition which, according to the Investigator, may result in undue risk of the patient by participating in the present study.
  17. 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): NCT03443674


Locations
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Australia, New South Wales
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Jennifer Aung    (02) 8738 9163    Jennifer.Aung@sswahs.nsw.gov.au   
Principal Investigator: Aflah Roohullah         
Orange Health Service Recruiting
Orange, New South Wales, Australia, 2800
Contact: Stephen Millard    02 6369 3127    Stephen.millard@health.nsw.gov.au   
Principal Investigator: Robert Zielinski         
Southern Medical Day Care Centre Recruiting
Wollongong, New South Wales, Australia, 2500
Contact: Sue Parker    +61 (0)2 4228 6200    sueparker.smdcctrials@outlook.com.au   
Principal Investigator: Morteza Aghmesheh         
Australia, Queensland
John Flynn Private Hospital Recruiting
Tugun, Queensland, Australia, 4224
Contact: Kenneth Musgrave    07 5598 9733    MusgraveK@ramsayhealth.com.au   
Principal Investigator: David Martin         
Australia, South Australia
Flinders Medical Centre Recruiting
Bedford Park, South Australia, Australia, 5042
Contact: Kelly Mead    61 08 8204 6151    kelly.mead@sa.gov.au   
Principal Investigator: Ganessan Kichenadasse         
Sponsors and Collaborators
Clover Biopharmaceuticals AUS Pty Ltd
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Responsible Party: Clover Biopharmaceuticals AUS Pty Ltd
ClinicalTrials.gov Identifier: NCT03443674    
Other Study ID Numbers: CLO-SCB-313-001
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020

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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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Neoplasms