A phase 1/2 study in which, DTX-SPL8783, the trial medication will beadministered (alone or in combination with nintedanib) in order to assess the safety, tolerability, pharmacokinetics (distribution of DTX-SPL8783 in the body) and efficacy in patients with advanced malignant tumours.
- Conditions
- ocally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC).MedDRA version: 20.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000877-19-GB
- Lead Sponsor
- Starpharma Pty Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 65
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:
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 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
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) < 1.5 × 109/L or platelet count < 100 × 109/L (cannot be post-transfusion) or haemoglobin < 9 g/dL (can be post- transfusion).
3.Serum bilirubin > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method