Patients with advanced solid tumours MedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: CTX-SPL9111
Product Code: CTX-SPL9111
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: CTX-SPL9111
CAS Number
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 curative therapy exists and who, in the opinion of the investigator, could potentially benefit from treatment with taxanes. 4. Measurable or evaluable disease per RECIST version 1.1., Prostate Cancer Working Group 3 (PCWG3) consensus guidelines (i.e. prostate cancer patients with bone-only lesions) or Response Assessment in Neuro- Oncology working group consensus guidelines (RANO; patients with primary central nervous system malignancy). 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life expectancy of greater than 12 weeks. 7. 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: - oral - intravaginal - transdermal ? progestogen-only hormonal contraception associated with inhibition of ovulation: - oral - 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 7.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 CTX-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 range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
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 MRI scan performed within the previous 4 weeks showing no tumour progression. 2. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count (ANC) upper limit of normal (ULN). 4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 1.5 × ULN. 5. 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. 6. History of a bleeding diathesis. 7. Allergy to cabazitaxel, other components of study therapy or compounds of similar chemical composition. 8. Congenital long-QT syndrome. 9. Myocardial infarction within 6 months of enrolment, congestive heart failure of New York Heart Association class > II, unstable angina or unstable cardiac arrhythmias. 10. Other uncontrolled intercurrent illness, including active infection. 11. A history of infection with HIV or hepatitis B or C viruses. 12. Participation in a study of an investigational agent within 30 days prior to first study therapy. 13. Anti-tumour therapy (including chemotherapy, radiation therapy, targeted therapeutics or hormonal therapy) within the 30 days prior to first study therapy. Permitted exceptions are concurrent use of GnRH agonists/antagonists for prostate cancer and radiation to bone metastases completed > 14 days prior to first study therapy. 14. Cumulative dose of corticosteroid = 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first IMP administration. 15. Unresolved toxicity from prior anti-tumour therapy, defined as toxicities (excluding alopecia) that have not resolved to < grade 2 as scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Exceptions may be allowed for stable toxicities after discussion with the investigator and sponsor. 16. Symptomatic grade 1 peripheral neuropathy. 17. Peripheral neuropathy of grade 2 or higher due to any cause. 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 (eg: history of poor diabetes control or non-compliance with anti-diabetic medication). 19. Major surgery within 30 days of commencing first study therapy. 20. Pregnant or breast-feeding females. 21. Concurrent or planned treatment with strong inhibitors (e.g. ketoconazole, itraconazo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of CTX-SPL9111 given intravenously (IV). ;Timepoint(s) of evaluation of this end point: Please refer to the study protocol.; Secondary Objective: - To characterise the safety and tolerability profile of CTX-SPL9111 in patients with advanced cancer - To characterise the pharmacokinetics (PK) of CTX-SPL9111 - To define a recommended dose for phase 2 studies of CTX-SPL9111 dosed IV - To explore preliminary anti-tumour efficacy ; Primary end point(s): 14.3 Endpoints 14.3.1 Safety endpoints Toxicity will be graded using the NCI CTCAE v4.03. Safety assessments will include medical review of AEs and the results of vital sign measurements, physical examinations, ECGs and clinical laboratory tests. 14.3.2 Pharmacokinetic Endpoints Plasma concentrations of free and total cabazitaxel 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. 14.3.3 Efficacy Endpoints RECIST 1.1 criteria, PCWG3 criteria and RANO criteria will be used to classify tumour responses to CTX-SPL9111 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): There are no secondary endpoints. ;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
United Kingdom
Contacts
Public ContactTheradex Regulatory
Theradex Oncology
Outcome results
None listed