|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|Patients with advanced solid tumours
|E.1.1.1||Medical condition in easily understood language ||
|Patients with advanced solid tumours
|E.1.1.2||Therapeutic area ||Diseases [C] - Cancer [C04]
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10007050
|E.1.2||System Organ Class ||100000004864
|E.1.3||Condition being studied is a rare disease || No
|E.2 Objective of the trial
|E.2.1||Main objective of the trial ||
|To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of CTX-SPL9111 given intravenously (IV).
|E.2.2||Secondary objectives of the trial ||
|- 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
- To explore preliminary anti-tumour efficacy
|E.2.3||Trial contains a sub-study || No
|E.3||Principal 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
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:
progestogen-only hormonal contraception associated with inhibition
intrauterine device (IUD)
intrauterine hormone-releasing system (IUS)
bilateral tubal occlusion
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.
|E.4||Principal 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
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 < 10 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.
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
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,
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) should
be avoided during CTX-SPL9111 treatment where possible. A 1-week
washout period is necessary for patients already on these treatments.
22. Any concurrent 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.
|E.5 End points
|E.5.1||Primary end point(s)||
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
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 the last observation for survival.
|E.5.1.1||Timepoint(s) of evaluation of this end point||
|Please refer to the study protocol.
|E.5.2||Secondary end point(s)||
|There are no secondary endpoints.
|E.5.2.1||Timepoint(s) of evaluation of this end point||
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| Yes
|E.7||Trial type and phase
|E.7.1||Human pharmacology (Phase I)|| Yes
|E.7.1.1||First administration to humans|| Yes
|E.7.1.2||Bioequivalence study|| No
|E.188.8.131.52||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| Yes
|E.7.3||Therapeutic confirmatory (Phase III)|| No
|E.7.4||Therapeutic use (Phase IV)|| No
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || No
|E.8.1.5||Parallel group|| No
|E.8.1.6||Cross over || No
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || No
|E.8.2.4||Number of treatment arms in the trial||1
The trial involves single site in the Member State concerned
|E.8.4|| The trial involves multiple sites in the Member State concerned || Yes
|E.8.4.1||Number of sites anticipated in Member State concerned||4
|E.8.5||The trial involves multiple Member States|| No
|E.8.6 Trial involving sites outside the EEA
|E.8.6.1||Trial being conducted both within and outside the EEA|| No
|E.8.6.2||Trial being conducted completely outside of the EEA|| No
|E.8.7||Trial has a data monitoring committee|| No
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|Last patient, last visit in the study.
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||2
|E.8.9.1||In the Member State concerned months||3
|E.8.9.1||In the Member State concerned days||0