A phase 1/2 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of SN38-SPL9111 (DEP®-SN38), a SN38 dendrimer conjugate, in patients with advanced solid tumours. - SN38-SPL9111 in advanced solid tumours

Starpharma Pty Ltd0 sites149 target enrollmentMay 9, 2019

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: Starpharma Pty Ltd
Enrollment: 149
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

May 9, 2019

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Starpharma Pty Ltd

Eligibility Criteria

Inclusion Criteria

•1\.Signed informed consent form.
•2\.At least 18 years old.
•3\. Patients with histologically or cytologically confirmed advanced or metastatic cancer for which no standard therapy is available and who in the opinion of the investigator, could potentially benefit from treatment with irinotecan or SN38\-SPL9111\. For phase 2 dose expansion, preference will be given to patients with colorectal, pancreatic, ovarian, upper gastrointestinal and breast cancers. Patients may also be irinotecan naïve. Exceptionally, tumours in other locations may be enrolled subject to sponsor approval.
•4\. Willing to be tested for uridine diphosphate\-glucuronosyl transferase 1 family, polypeptide A1 (UGT1A1\) genotype (if this result is not already available).
•5\. Measurable disease per RECIST version 1\.1 or applicable radiological or biochemical assessment. In the dose escalation/ assessment parts, patients with measurable or evaluable disease will be enrolled; in the dose expansion parts, only patients with measurable disease will be enrolled.
•6\.Adequate bone marrow reserve as demonstrated by an absolute neutrophil count (ANC) \= 1\.5 × 109/L or platelet count \= 100 × 109/L (cannot be post\-transfusion) or haemoglobin \= 9 g/dL (can be post\-transfusion).
•7\.Serum bilirubin \< 1\.5 x upper limit of normal (ULN)
•8\.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \< 2\.5 × ULN or \< 5x ULN for patients with liver metastases
•9\.Serum creatinine \< 1\.5 × ULN; however, an exception can be made if the calculated (by the Cockcroft\-Gault formula) or measured creatinine clearance is \> 50 mL/min.
•10\.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\.

Exclusion Criteria

•1\.Uncontrolled brain metastases or spinal cord compression. Patients who were treated with surgical resection or radiation therapy completing at least 4 weeks earlier are eligible if they are neurologically stable and have a follow\-up Magnetic Resonance Imaging (MRI) scan performed within the previous 4 weeks showing no tumour progression.
•2\.Patients homozygous for the UGT1A1\*28 allele (Gilbert syndrome) or patients with a congenital deficiency of UGT1A1 (Crigler\-Najjar syndrome) will be excluded from the Phase 1 dose\-escalation/ dose assessment part of the study; they may be enrolled in the Phase 2 dose expansions part starting at a reduced dose and incrementing to the full recommended dose, if no excessive toxicity is encounted.
•3\.History of an untreated bleeding diathesis.
•4\.Active bowel obstruction, history of inflammatory bowel disease or chronic or acute gastrointestinal disorders with diarrhoea as a major symptom.
•5\.Allergy/hypersensitivity to irinotecan and SN38\-containing preparations, pegylated drugs or other components of study therapy or compounds of similar chemical composition.
•6\.Myocardial infarction within 6 months of enrolment, congestive heart failure of New York Heart Association class \> II, unstable angina or unstable cardiac arrhythmias.
•7\. Other uncontrolled intercurrent illness, including active infection.
•8\. Participation in a study of an investigational agent within 30 days prior to first dose of study therapy.
•9\. Anti\-tumour therapy (including chemotherapy, radiation therapy, targeted therapeutics or hormonal therapy) within 28 days or 5\-half\-lives (whichever is shorter) prior to first study therapy.
•10\. Cumulative dose of corticosteroid \= 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks of the first IMP administration.