Advanced malignant solid tumours MedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: DTX-SPL8783
Product Code: DTX-SPL8783
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DTX-SPL8783
CAS Number: 148408-66-6
Current Sponsor code: DTX-SPL8783
Oth
Sponsors
Starpharma Pty Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 or applicable radiological and/or biochemical assessment with relevant serum tumour markers e.g., CA-19-9, CA-125, prostate specific antigen PSA, carcinoembryonic antigen . 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3. Life expectancy of greater than 12 weeks. 4. Signed informed consent form. 5. At least 18 years old. 6. Reproductive inclusion criteria : a) If of childbearing potential, willing to use an effective form of contraception (see below) during 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: - oral - intravaginal - transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: - oral - injectable - implantable • 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 8.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 DTX-SPL8783 until 6 months after their final dose, to protect their partner from exposure to study drug. Arm-Specific Inclusion Criteria Gemcitabine Combination 1. Patients should have histologically or cytologically confirmed locally advanced, metastatic or locally recurrent cancer for which gemcitabine and/or a taxane such as docetaxel is considered a treatment option. Preference will be given to gemcitabine-naïve patients in locally advanced or metastatic setting with pancreatic ductal adenocarcinoma. 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 range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Symptomatic brain metastases or imminent untreated spinal cord compression. Patients who were treated with surgical resection or radiation therapy completing at least 4 weeks prior to enrolment are not excluded if they are neurologically stable, not taking glucocorticoids and are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening). 2. Taxane chemotherapy (e.g., docetaxel, paclitaxel) in the previous 6 months. 3. Inadequate bone marrow reserve as demonstrated by: • an absolute neutrophil count (ANC) upper limit of normal (ULN). 5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 1.5 × ULN; or AST or ALT > 2.5 × ULN irrespective of ALP level. 6. Serum creatinine > 1.5 × ULN; however, an exception can be made if the calculated clearance (by the Cockcroft-Gault formula) or measured creatinine clearance is > 50 mL/min. 7. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) > 1.5 × ULN that cannot be explained due to concomitant medication. 8. Use of therapeutic anticoagulation, with the exception of treatment with a low molecular weight heparin. 9. History of an untreated bleeding diathesis. 10. Allergy to docetaxel, other components of study therapy or compounds of similar chemical composition. 11. Hypersensitivity to gemcitabine, or to any of the excipients listed in the SPCs. 12. Congenital long-QT syndrome. 13. Myocardial infarction within 6 months of enrolment, congestive heart failure of New York Heart Association class > II, unstable angina or unstable cardiac arrhythmias. 14. Administration of any investigational agent within 30 days prior to study therapy. 15. Anti-tumour therapy (including chemotherapy, radiation therapy, targeted therapeutics or hormonal therapy) within the 30 days or 5 half-lives (whichever is the shorter) prior to first study therapy. Permitted exceptions are concurrent use of Gonadotropin releasing hormone (GnRH) agonists for prostate cancer and radiation to bone metastases completed > 14 days prior to first study therapy. 16. Unresolved toxicity from prior anti-tumour therapy, defined as toxicities (excluding alopecia) that have not resolved to < grade 2 as graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Exceptions may be allowed for stable toxicities after discussion with the investigator and sponsor. 17. Peripheral neuropathy of grade 2 or higher due to any cause other than the cancer under investigation. 18. Patients with diabetes with signs or symptoms of peripheral neuropathy or other end organ damage or those at a higher risk of peripheral neuropathy (e.g.: history of poor diabetes control or non-compliance with anti-diabetic medication). 19. Concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4/5. Concurrent or planned treatment with Organic Anion-Transporting-Polypeptide-1B3 (OATP1B3) substrates (e.g., statins, valsartan, repaglinide, amlodipine and other calcium channel blockers of the same class) should be avoided during DTX-SPL8783 treatment where possible. A 1-week washout period is necessary for patients already on any of these treatments. (Refer to Section 7.3 f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Ongoing;Main Objective: To characterise the safety and tolerability profile of DTX-SPL8783 in combination with anti-cancer agents in patients with advanced malignancies ;Primary end point(s): Safety and tolerability as reflected by NCI CTCAE v5.0 grading of toxicities. Safety assessments will include medical review of AEs and the results of vital sign measurements, physical examinations, ECGs and clinical laboratory tests.;Secondary Objective: • To assess the clinical utility of DTX-SPL8783 when administered in combination with anti-cancer agents in patients with advanced malignancies • To characterise the pharmacokinetics (PK) of DTX-SPL8783 in combination with anti-cancer agents in blood and tumour tissue samples • To determine the treatment dose for the combination of DTX-SPL8783 and anti-cancer agents • To explore preliminary anti-tumour efficacy of DTX-SPL8783 combination therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic Endpoints Plasma concentrations of free and total docetaxel 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 DTX-SPL8783 into the following categories: (1) complete response; (2) partial response; (3) stable disease; or (4) progressive disease. The following efficacy variables will be derived: • Objective Response Rate (ORR) based on RECIST 1.1 • 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 at the last observation for survival. Serum tumour markers relevant to the tumour type and skin tumours or subcutaneous metastases will also be measured during screening, day 1 of every dose cycle (+/- 7 days) from cycle 2 and at the End of Study visit.;Timepoint(s) of evaluation of this end point: PK: For the first DTX-SPL8783 infusion (Cycle 1), PK blood samples will be collected immediately before infusion (pre-infusion) and at the end of infusion (EOI, which will be approximately 60 minutes after start of infusion (SOI) and then at 1, 3, 5, and 23 (Day 2) hours post-EOI. Blood samples will also be collected on Day 8 and Day 15 of the first cycle. In cycles 2-4, PK samples will then be collected at one time-point: pre-infusion and then end of study. Tumour assessments: Physical exam and tumour marker assessment (if applicable) occurs every cycle; radiographic assessment | — |
Countries
United Kingdom
Contacts
Public ContactPhilip van der Veen
Theradex Oncology Ltd
Outcome results
None listed