A Phase I Study Evaluating SCB-313 for the Treatment of Subjects With Peritoneal Carcinomatosis
Study Details
Study Description
Brief Summary
To evaluate the safety and tolerability of SCB-313 in patients with peritoneal carcinomatosisa, to determine the maximum tolerated dose (MTD) and/or extended study recommended dose (RDE) for SCB-313 intraperitoneal injection, providing a basis for dosing regimen and dose choosing in clinical trial subsequently.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SCB-313
|
Drug: SCB-313
Intraperitoneal injection, 3 doses on D1,D4,D7，21 days for 1 cycle
Other Names:
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Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicity (DLT) [21 days after first dosing]
DLT
- Occurrence of adverse events (AEs) and serious adverse events (SAEs) [21 days after first dosing]
AEs
Secondary Outcome Measures
- Immunogenicity [28 days after last dosing]
Occurrence of binding and neutralizing anti-SCB-313 antibodies
- Pharmacokinetics (Cmax) [Up to 24 hours after dosing]
Maximum SCB-313 concentration
- Pharmacokinetics (tmax) [Up to 24 hours after dosing]
Time to Cmax of SCB-313
- Pharmacokinetics ([AUC]0-24) [Up to 24 hours after dosing]
Area under SCB-313 concentration time curve from zero to 24 hours
- Pharmacokinetics (AUC 0-inf) [Up to 24 hours after dosing]
Area under curve from time 0 extrapolated to infinity
Eligibility Criteria
Criteria
Inclusion Criteria:
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Be able to understand and voluntarily sign written informed consent.
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Male or female subjects, age ≥18, ≤75 years.
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Confirmed by histopathology or cytopathology, any primary or secondary malignant peritoneal carcinomatosis subject.
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Progression after standard treatment, or inability to tolerate standard treatment, or no standard treatment.
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ECOG status 0 to 2 or KPS status > 60
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CT-PCI (Peritoneal Carcinomatosis Index) status ≥ 15
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Life expectancy of at least 3 months.
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No serious hematologic, hepatic, renal dysfunction, comply with the following laboratory test results:
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Hematology: white blood cell count >3109/L, absolute neutrophil count ≥1.5109/L, platelets > 75*109/L, hemoglobin > 90 g/L.
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Liver function: aspartate aminotransferase and alanine aminotransferase ≤ 3 times ULN, Alkaline phosphatase (ALP) ≤ 2.5 times ULN; serum total bilirubin (TBIL) ≤ 1.5 times ULN.
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Renal function: Creatinine clearance calculated according to the Cockcroft-Gault formula ≥ 50 mL/min.
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All adverse events from previous system anticancer treatment return to baseline or ≤ grade 1 (except for alopecia and vitiligo, neuropathy which induced by previous anticancer therapy status stable or ≤ grade 2).
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Male or female subjects undergo effective contraception during treatment and within 6 months after last dose.
Exclusion Criteria:
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Previous treatment with TRAIL pathway drug.
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Malignant cancer diseases other than malignant peritoneal carcinomatosis in this study (Exceptions include: a cured malignant cancer without relapse within 3 years prior to the study enrollment, completely resected basal cells and squamous cell skin cancer, and any type of carcinoma in situ).
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Primary lesion invades the central nervous system (CNS) with symptoms develop, status unstable or require high dose steroids (e.g. dexamethasone ≥ 10 mg or equivalent dose) to control.
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Abnormal HBV examination, anti-HCV positive, anti-HIV antibody positive or other serious infections requiring systemic treatment within 4 weeks prior to first dosing (e.g. virus, bacteria or fungus).
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Use the following concomitant therapy before dosing:
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Use drug that prolongs the QT interval and/or associated with the risk of torsades de pointes ventricular tachycardia (TdP) within 7 days prior to first dosing.
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Use amiodarone within 90 days prior to first dosing.
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Impaired heart function or clinically significant cardiovascular disease, including any of the following:
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Cerebrovascular accident/stroke (within 6 months prior to enrollment).
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Myocardial infarction (within 6 months prior to enrollment).
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Unstable angina, congestive heart failure (New York Heart Association grade ≥ II) or severe arrhythmia requiring medication (including QT/QTc interval extension
480 msec, installation of pacemakers, etc.).
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Left ventricular ejection fraction < 50% as determined by echocardiography.
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Active bleeding history or gastrointestinal perforation risk within 4 weeks before enrollment, or not healed from recent surgery.
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Received anticancer treatment within following specified time before first dosing:
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Received medical treatment ≤ 4 weeks or 5 times known drug half-life (whichever is longer).
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Underwent major surgery within ≤ 4 weeks before first dosing.
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Residual adverse events from previous treatment≥ grade 2.
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Known to have alcohol and/or drug dependence.
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Previous clear history of neurological or mental disorders, such as epilepsy, poor compliance
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Female subjects with positive blood pregnancy tests or during lactation.
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Previously allergic to macromolecular protein drugs or proteins or Quincke's edema (Kunke edema, also known as angioedema) or allergic to any component of the SCB 313.
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Known history of infection with human immunodeficiency virus, or other acquired, innate immune deficiency diseases, or history of organ transplantation.
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Vaccination within ≤ 4 weeks prior to first dosing, or planning live vaccination.
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For other reasons according to investigators, not suitable for participation in the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Shijitan Hospital Capital Medical University | Beijing | Beijing | China | 100038 |
Sponsors and Collaborators
- Sichuan Clover Biopharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLO-SCB-313-CHN-003