Advanced solid tumours. MedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: DEP™-SN38
Product Code: SN38-SPL9111
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: SN38-SPL9111
Current Sponsor code: SN38-SPL9111
Other descriptive name: SN38-SPL9111
Co
Sponsors
Starpharma Pty Ltd
Eligibility
Sex/Gender
All
Inclusion 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 50 mL/min. 10.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 11.Life expectancy of greater than 12 weeks. 12.Reproductive inclusion criteria: a)If of childbearing potential, willing to use an effective form of contraception (see below) during chemotherapy treatment and for at least six months thereafter. Such methods include (if using hormonal contraception this method must be supplemented with a barrier method, preferably male condom): •combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: ooral ointravaginal otransdermal •progestogen-only hormonal contraception associated with inhibition of ovulation: ooral oinjectable oimplantable •intrauterine device (IUD) •intrauterine hormone-releasing system (IUS) •bilateral tubal occlusion •vasectomised partner •true sexual abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception. b) Women must have a negative pregnancy test at study entry. c) Men who are truly sexually abstinent when this is in line with the preferred and usual lifestyle of the subject or vasectomized or willing to ensure that their female sexual partners use a highly-effective means of contraception (i.e. as outlined in Inclusion criterion 12.a.) for the duration of study therapy and 6 months afterwards. In addition, men must be willing to use a condom during sexual intercourse from the first dose of SN38-SPL9111 until 6 months after their final dose, so as to protect their partner from exposure to study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age ra
Exclusion criteria
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. 11. Unresolved toxicity from prior anti-tumour therapy, defined as toxicities (excluding alopecia) that have not resolved to < grade 2 or baseline as scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Exceptions may be allowed for stable toxicities after investigator discussion with the Medical Monitor and sponsor. 12. Major surgery within 28 days of commencing first dose of study therapy. 13. Pregnant or breast-feeding females. 14. Concurrent or planned treatment with strong inhibitors of UDP-Glucuronosyl transferase 1A1 (UGT1A1) (e.g., atazanavir, gemfibrozil, indinavir). A 1-week washout period is necessary for patients already on these treatments. 15. Any concurrent, clinically significant condition which, in the Investigator's opinion, makes it undesirable for the subject to participate in this study or which would jeopardize compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of SN38-SPL9111 given intravenously (IV);Secondary Objective: To characterise the safety and tolerability profile of SN38-SPL9111 in patients with advanced cancer To characterise the pharmacokinetics (PK) of SN38-SPL9111 and SN38 To define a recommended dose for phase 2 studies of SN38-SPL9111 dosed IV To explore preliminary anti-tumour efficacy;Primary end point(s): The primary outcome for the study is safety. Safety assessments will include medical review of AEs and the results of vital sign measurements, physical examinations, ECGs and clinical laboratory tests. Toxicity will be graded using the NCI CTCAE v 5.0 scale.;Timepoint(s) of evaluation of this end point: Last patient last visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic Endpoints Plasma concentrations of free and total SN38-SPL9111 versus time will be analysed using non-compartmental methods and a validated PK analysis program to generate the following PK parameters for each patient: Cmax: Maximum observed plasma concentration. Tmax: Time to maximum observed plasma concentration. AUC: Area under the concentration-time curve. t1/2: Apparent terminal half-life. Efficacy Endpoints RECIST 1.1 criteria will be used to classify tumour responses to SN38-SPL9111 into the following categories: (1) complete response; (2) partial response; (3) stable disease; or (4) progressive disease. Where RECIST is not applicable, relevant radiological or biochemical evaluation criteria based on the cancer type and a modality generally accepted for its assessment will be used following consultation between the investigator and the sponsor’s medical monitor. The following efficacy variables will be derived: •Objective Response Rate (ORR) •Progression Free Survival (PFS) which equals time from enrolment to progression or death whichever comes first •Overall Survival (OS) which equals time from enrolment to death •Duration of best overall response •Duration of stable disease If progression or death are not observed then the time will be censored at the last tumour assessment for PFS, and the last observation for survival.;Timepoint(s) of evaluation of this end point: Last patient last visit | — |
Countries
Australia, United Kingdom
Contacts
Public ContactClinical Development
Starpharma Pty Ltd
Outcome results
None listed