Locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC). MedDRA version: 20.0 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: DTX-SPL8783
Product Code: Concentrate for solution for infusion
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: DTX-SPL8783
Current Sponsor code
Sponsors
Starpharma Pty Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form. 2. At least 18 years old. 3. Histologically or cytologically confirmed advanced or metastatic cancer for which no standard or curative therapy exists. For patients selected to be treated with the nintedanib combination, they should have locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after first-line chemotherapy. 4. No taxane chemotherapy (eg. docetaxel, paclitaxel) in the previous 6 months. 5. Measurable or evaluable disease per RECIST version 1.1 or applicable radiological or biochemical assessment. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy of greater than 12 weeks. 8. 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: o oral o intravaginal o transdermal progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o 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 with female sexual partners (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, 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 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
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 prior to enrolment are not excluded if they are neurologically stable, not taking glucocorticoids 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 in conjunction with alkaline phosphatase > 2.5 × ULN; or AST or ALT > 2.5 × ULN irrespective of alkaline phosphatase level. 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. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) > 1.5 × ULN. 7. Use of therapeutic anticoagulation, with the exception of treatment with a low molecular weight heparin. 8. History of a bleeding diathesis. 9. Allergy to docetaxel, other components of study therapy or compounds of similar chemical composition. 10. Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients listed in the SPC. 11. Congenital long-QT syndrome. 12. Myocardial infarction within 6 months of enrolment, congestive heart failure of New York Heart Association class > II, unstable angina or unstable cardiac arrhythmias. 13. Other uncontrolled intercurrent illness, including active infection. 14. A history of infection with HIV or hepatitis B or C viruses. 15. Participation in a study of an investigational agent within 30 days prior to first study therapy. 16. 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 for prostate cancer and radiation to bone metastases completed > 14 days prior to first study therapy. 17. 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 4.03. Exceptions may be allowed for stable toxicities after discussion with the investigator and sponsor. 18. Peripheral neuropathy of grade 2 or higher due to any cause other than the cancer under investigation. 19. 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). 20. Concurrent or planned treatment with strong inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) or inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital) of cytochrome P450 3A4/5. Concurrent or planned treatment with St John’s Wort. Concurrent or planned treatment with Organic Anion-Transporting-Polypeptide OATP1B1 substrates (e.g, statins, valsartan, repaglinide, amlodipine and other calcium channel blockers of the same class) should be avoided during DTX-SPL8783 treatm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the maximum tolerated dose and dose-limiting toxicities of DTX-SPL8783 given intravenously (IV). ;Secondary Objective: • To characterise the safety and tolerability profile of DTX-SPL8783 in patients with advanced cancer • To characterise the pharmacokinetics of DTX-SPL8783 in blood and tumour tissue samples • To define a recommended dose for clinical studies of DTX-SPL8783 dosed intravenously (IV) • To assess the safety of DTX-SPL8783 and nintedanib combination therapy • To explore preliminary anti-tumour efficacy;Primary end point(s): 14.3.1 Safety endpoints Toxicity will be graded using the NCI CTCAE v4.0. 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 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 14.3.3 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 responses 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.;Timepoint(s) of evaluation of this | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): There are no secondary endpoints. ;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Australia, United Kingdom
Contacts
Public ContactMarie Moores
Theradex Oncology
Outcome results
None listed