Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 : August 3, 2018
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 daily over 3 days via IP bolus injection for the treatment of cancer patients with recurrent refractory malignant ascites.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 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 Ascites
Actual Study Start Date : June 18, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Arm Intervention/treatment
Experimental: SCB-313
Dose Escalation - 5 Sequential Dose Cohorts.
Drug: SCB-313
3 intraperitoneal injections of SCB-313 on Days 1, 2 and 3
Other Name: recombinant human TRAIL-Trimer fusion protein




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

  2. Ratio of Ascites Flow Rate on Day 4 (Post-Therapy) / Baseline [ Time Frame: Assessment on baseline and day 4 ]

Secondary Outcome Measures :
  1. Safety: Occurrence of serious adverse events (SAEs) and/or treatment emergent adverse events (TEAEs) [ Time Frame: 30 days after start of treatment ]
    Occurrence of serious adverse events (SAEs) and/or treatment emergent adverse events (TEAEs)

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

  3. Ratio of puncture-free interval post therapy / baseline [ Time Frame: Up to 6 months after start of treatment ]
  4. Puncture free survival [ Time Frame: Up to 6 months after start of treatment ]
  5. Puncture-free rate Day 30 [ Time Frame: 30 days after start of treatment ]
  6. Change in Ascites Flow Rate versus baseline [ Time Frame: Days 2, 3 and up to 6 months after start of treatment ]
  7. Changes in 24-hour urine volume [ Time Frame: Assessment on baseline and days 1-4 ]
  8. Changes in GFR [ Time Frame: Assessment on baseline and days 1-4 ]
  9. Overall survival [ Time Frame: Up to 6 months after start of treatment ]
  10. PuFS rate at Day 30 [ Time Frame: 30 days after start of treatment ]
  11. Pharmacokinetics (Cmax) [ Time Frame: Up to 1 day after start of treatment ]
    Maximum SCB-313 concentration

  12. Pharmacokinetics (Cmax/D) [ Time Frame: Up to 1 day after start of treatment ]
    Dose-normalized Cmax of SCB-313

  13. Pharmacokinetics (tmax) [ Time Frame: Up to 1 day after start of treatment ]
    Time to Cmax of SCB-313

  14. Pharmacokinetics ([AUC]0-24) [ Time Frame: Up to 1 day after start of treatment ]
    Area under SCB-313 concentration time curve from zero to 24 hours

  15. Pharmacokinetics (AUC0-24/D) [ Time Frame: 1 day after start of treatment ]
    Dose-normalized AUC0-24 of SCB-313

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

  17. Pharmacokinetics (Ctrough) [ Time Frame: Up to 3 days after start of treatment ]
    Trough concentration of SCB-313 at each predose and at 24 hours after the last dose

  18. Pharmacokinetics (Amount of drug in ascites after 24 hours of each dose) [ Time Frame: Up to 3 days after start of treatment ]
    Amount of SCB-313 in ascites after 24 hours of each dose.

  19. Pharmacokinetics (AUC0-last) [ Time Frame: Up to 10 days after start of treatment ]
    AUC from time 0 on Day 1 to the last quantifiable concentration time point after dosing on Day 3 (Final PK sample time point on Day 10)

  20. Pharmacokinetics (AUC 0-inf) [ Time Frame: Up to 10 days after start of treatment ]
    Area under curve from time 0 extrapolated to infinity

  21. Pharmacokinetics (AUC0-inf/D) [ Time Frame: Up to 10 days after start of treatment ]
    Dose-normalized AUC0-inf

  22. Pharmacokinetics (t1/2) [ Time Frame: Up to 10 days after start of treatment ]
    Terminal half-life (Final PK sample time point on Day 10)

  23. Pharmacokinetics (CL/F) [ Time Frame: Up to 10 days after start of treatment ]
    Apparent systemic clearance after dosing intraperitoneally (Final PK sample time point on Day 10)

  24. Pharmacokinetics (Vz/F) [ Time Frame: Up to 10 days after start of treatment ]
    Apparent volume of distribution after dosing intraperitoneally (Final PK sample time point on Day 10)

  25. Pharmacokinetics (λz) [ Time Frame: Up to 10 days after start of treatment ]
    Terminal rate constant (Final PK sample time point on Day 10)

  26. Pharmacokinetics (Cmax ascites/serum ratio) [ Time Frame: Up to 10 days after start of treatment ]
    Ascites/serum exposure ratios for Cmax. (Final PK sample time point on Day 10)

  27. Pharmacokinetics (AUC0-24 ascites/serum ratio) [ Time Frame: Up to 10 days after start of treatment ]
    Ascites/serum exposure ratios for AUC0-24. (Final PK sample time point on Day 10)

  28. Pharmacokinetics (AUC0-inf ascites/serum ratio) [ Time Frame: Up to 10 days after start of treatment ]
    Ascites/serum exposure ratios for AUC0-inf. (Final PK sample time point on Day 10)

  29. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    anorexia; using a 4-point Likert scale (none, mild, moderate, and severe)

  30. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    nausea; using a 4-point Likert scale (none, mild, moderate, and severe)

  31. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    early satiety; using a 4-point Likert scale (none, mild, moderate, and severe)

  32. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    vomiting; using a 4-point Likert scale (none, mild, moderate, and severe)

  33. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    abdominal pain; using a 4-point Likert scale (none, mild, moderate, and severe)

  34. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    abdominal swelling; using a 4-point Likert scale (none, mild, moderate, and severe)

  35. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    dyspnea; using a 4-point Likert scale (none, mild, moderate, and severe)

  36. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    fatigue; using a 4-point Likert scale (none, mild, moderate, and severe)

  37. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    swollen ankles; using a 4-point Likert scale (none, mild, moderate, and severe)

  38. Changes in ascites-related symptoms [ Time Frame: Up to 60 days after start of treatment ]
    heartburn; using a 4-point Likert scale (none, mild, moderate, and severe)


Other Outcome Measures:
  1. Tumor response [ Time Frame: Up to 6 months after start of treatment ]
    In patients with measurable disease using RECISTv1.1 as applicable

  2. Changes in serum tumor markers [ Time Frame: Up to 6 months after start of treatment ]
    CEA

  3. Changes in serum tumor markers [ Time Frame: Up to 6 months after start of treatment ]
    CA-125

  4. Changes in serum tumor markers [ Time Frame: Up to 6 months after start of treatment ]
    CA-19-9

  5. Changes in tumor cell count in ascites [ Time Frame: Assessment on baseline and days 1-4 ]
  6. Quality of Life [ Time Frame: Up to 60 days after start of treatment ]
    Assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30); using 4-point Likert scale (Min Value: Excellent / Max Value: Poor)

  7. Changes in serum PD biomarkers [ Time Frame: Up to 10 days after start of treatment ]
    Caspase-cleaved cytokeratin 18 (CK-18)

  8. Predictive biomarker analysis [ Time Frame: Baseline ]
    KRAS mutation (assessed using archival tumor specimens and ascites samples)

  9. Predictive biomarker analysis [ Time Frame: Baseline ]
    MMR defects (assessed using archival tumor specimens and ascites samples)

  10. Predictive biomarker analysis [ Time Frame: Baseline ]
    Bcl2 overexpression (assessed using archival tumor specimens and ascites samples)

  11. Predictive biomarker analysis [ Time Frame: Baseline ]
    TRAIL resistance (assessed using archival tumor specimens and ascites 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.


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

Inclusion Criteria:

  • Histologically or cytologically confirmed refractory cancer after failure or refusal of all approved therapies, and no better option available in the Investigator's opinion.
  • Any type of solid tumor up to DL4, and only GI cancer or OC for DL5 and the expansion cohorts (if applicable).
  • Evidence of recurrent refractory symptomatic malignant ascites in the peritoneal cavity amenable to full drainage and having required at least 2 prior paracenteses at ≤ 45 day interval before screening or having an ascites flow rate of ≥ 10 mL/hour before screening (measured over at least a 24 hour period).
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 3.
  • Life expectancy of at least 8 weeks.
  • Age ≥ 18 years.
  • Body weight ≥ 45 kg.
  • Adequate hematological function, defined as: (a) Platelet count ≥ 100,000/µL, (b) Prothrombin time and activated partial thromboplastin time ≤ 1.5 times the upper limit of normal (ULN), (c) Absolute neutrophil count ≥ 1,000/µL, and (d) Hemoglobin ≥ 10 g/dL for men and 9 g/dL for women, without the need for transfusion in the 2 weeks prior to screening.
  • Adequate renal function, defined as serum creatinine ≤ 2.0 times ULN and creatinine clearance > 50 mL/minute.
  • Adequate liver function, defined as: (a) Aspartate aminotransferase and alanine aminotransferase ≤ 3 times ULN for patients without liver metastases, or ≤ 5 times ULN in the presence of liver metastases, and (b) Bilirubin ≤ 2.0 times ULN, unless patient has known Gilbert's syndrome.
  • Female patients of child bearing potential (excluding women who have undergone surgical sterilization or menopause.
  • Willing to attend follow-up visits on Day 10, 20 and 30 after the first study drug administration.

Exclusion Criteria:

  • Loculated ascites not amenable to full drainage.
  • Acute or chronic infection (such as tuberculosis) requiring antiviral or intravenous antibiotics within 2 weeks prior to enrollment.
  • Symptoms or signs (including laboratory tests) of clinically significant concomitant hematologic, cardiovascular, pulmonary, hepatic, renal, pancreatic, or endocrine diseases.
  • Body mass index < 17 kg/m2.
  • Residual adverse events (AEs) > Grade 2 from previous treatment except alopecia.
  • 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 >450 msec at baseline.
  • Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg confirmed upon repeated measures.
  • Left ventricular ejection fraction < 40% as determined by echocardiography performed at screening or within 90 days prior to enrollment.
  • Prior anti-tumor therapy (chemotherapy) within 2 weeks, hormone therapy or palliative extra abdominal radiotherapy within at least 1 week, or molecular 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 DLT evaluation period after SCB 313 therapy.
  • Major surgery within 4 weeks prior to enrollment.
  • Patient with ileus within 30 days prior to screening.
  • Known portal vein obstruction (due to either prehepatic, hepatic, or posthepatic condition) which per Investigator's judgement, is the primary or significant cause of ascites.
  • Positive serology test for human immunodeficiency virus type 1 and 2, or known history of other immunodeficiency disease.
  • Albumin < 2.8 g/dL (the patient can receive albumin to meet the criterion).
  • Live vaccine within 2 weeks prior to enrollment.
  • Scheduled participation in another clinical study involving an investigational product or device during the course of this study.
  • Previous treatment with a TRAIL-based therapy or Death Receptor (DR) 4/5 agonist therapy.
  • Known or suspected hypersensitivity to any component of the SCB 313.
  • Any further condition which, according to 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.

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
Layout table for location information
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, Wollongong Private Hospital 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
Mater Misericordiae Limited Recruiting
South Brisbane, Queensland, Australia, 4101
Contact: David Courtney-Rodgers    07 3163 1396    david.courtney-rodgers@mater.org.au   
Principal Investigator: Catherine Shannon         
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 Not yet recruiting
Bedford Park, South Australia, Australia, 5042
Principal Investigator: Ganessan Kichenadasse         
Sponsors and Collaborators
Clover Biopharmaceuticals AUS Pty Ltd

Layout table for additonal information
Responsible Party: Clover Biopharmaceuticals AUS Pty Ltd
ClinicalTrials.gov Identifier: NCT03443674     History of Changes
Other Study ID Numbers: CLO-SCB-313-001
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: July 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Ascites
Pathologic Processes