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

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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

Tracking Information
First Submitted Date  ICMJE January 7, 2018
First Posted Date  ICMJE February 23, 2018
Last Update Posted Date August 3, 2018
Actual Study Start Date  ICMJE June 18, 2018
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2018)
  • Dose Limiting Toxicity (DLT) [ Time Frame: 30 days after start of treatment ]
    Occurrence of dose limiting toxicity (DLT)
  • Ratio of Ascites Flow Rate on Day 4 (Post-Therapy) / Baseline [ Time Frame: Assessment on baseline and day 4 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03443674 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2018)
  • 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)
  • 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
  • Ratio of puncture-free interval post therapy / baseline [ Time Frame: Up to 6 months after start of treatment ]
  • Puncture free survival [ Time Frame: Up to 6 months after start of treatment ]
  • Puncture-free rate Day 30 [ Time Frame: 30 days after start of treatment ]
  • Change in Ascites Flow Rate versus baseline [ Time Frame: Days 2, 3 and up to 6 months after start of treatment ]
  • Changes in 24-hour urine volume [ Time Frame: Assessment on baseline and days 1-4 ]
  • Changes in GFR [ Time Frame: Assessment on baseline and days 1-4 ]
  • Overall survival [ Time Frame: Up to 6 months after start of treatment ]
  • PuFS rate at Day 30 [ Time Frame: 30 days after start of treatment ]
  • Pharmacokinetics (Cmax) [ Time Frame: Up to 1 day after start of treatment ]
    Maximum SCB-313 concentration
  • Pharmacokinetics (Cmax/D) [ Time Frame: Up to 1 day after start of treatment ]
    Dose-normalized Cmax of SCB-313
  • Pharmacokinetics (tmax) [ Time Frame: Up to 1 day after start of treatment ]
    Time to Cmax of SCB-313
  • 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
  • Pharmacokinetics (AUC0-24/D) [ Time Frame: 1 day after start of treatment ]
    Dose-normalized AUC0-24 of SCB-313
  • 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
  • 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
  • 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.
  • 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)
  • Pharmacokinetics (AUC 0-inf) [ Time Frame: Up to 10 days after start of treatment ]
    Area under curve from time 0 extrapolated to infinity
  • Pharmacokinetics (AUC0-inf/D) [ Time Frame: Up to 10 days after start of treatment ]
    Dose-normalized AUC0-inf
  • Pharmacokinetics (t1/2) [ Time Frame: Up to 10 days after start of treatment ]
    Terminal half-life (Final PK sample time point on Day 10)
  • 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)
  • 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)
  • Pharmacokinetics (λz) [ Time Frame: Up to 10 days after start of treatment ]
    Terminal rate constant (Final PK sample time point on Day 10)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 18, 2018)
  • Tumor response [ Time Frame: Up to 6 months after start of treatment ]
    In patients with measurable disease using RECISTv1.1 as applicable
  • Changes in serum tumor markers [ Time Frame: Up to 6 months after start of treatment ]
    CEA
  • Changes in serum tumor markers [ Time Frame: Up to 6 months after start of treatment ]
    CA-125
  • Changes in serum tumor markers [ Time Frame: Up to 6 months after start of treatment ]
    CA-19-9
  • Changes in tumor cell count in ascites [ Time Frame: Assessment on baseline and days 1-4 ]
  • 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)
  • Changes in serum PD biomarkers [ Time Frame: Up to 10 days after start of treatment ]
    Caspase-cleaved cytokeratin 18 (CK-18)
  • Predictive biomarker analysis [ Time Frame: Baseline ]
    KRAS mutation (assessed using archival tumor specimens and ascites samples)
  • Predictive biomarker analysis [ Time Frame: Baseline ]
    MMR defects (assessed using archival tumor specimens and ascites samples)
  • Predictive biomarker analysis [ Time Frame: Baseline ]
    Bcl2 overexpression (assessed using archival tumor specimens and ascites samples)
  • Predictive biomarker analysis [ Time Frame: Baseline ]
    TRAIL resistance (assessed using archival tumor specimens and ascites samples)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study With SCB-313 (Recombinant Human TRAIL-Trimer Fusion Protein) for Treatment of Malignant Ascites
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Ascites
Intervention  ICMJE Drug: SCB-313
3 intraperitoneal injections of SCB-313 on Days 1, 2 and 3
Other Name: recombinant human TRAIL-Trimer fusion protein
Study Arms  ICMJE Experimental: SCB-313
Dose Escalation - 5 Sequential Dose Cohorts.
Intervention: Drug: SCB-313
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 18, 2018)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03443674
Other Study ID Numbers  ICMJE CLO-SCB-313-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Clover Biopharmaceuticals AUS Pty Ltd
Study Sponsor  ICMJE Clover Biopharmaceuticals AUS Pty Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Clover Biopharmaceuticals AUS Pty Ltd
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP