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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03600467




Registration number
NCT03600467
Ethics application status
Date submitted
22/06/2018
Date registered
26/07/2018
Date last updated
18/09/2019

Titles & IDs
Public title
Activity of Seviteronel in Patients With Androgen Receptor (AR)-Positive Glioblastoma
Scientific title
A Single-arm, Open-label, Signal-seeking, Phase IIa Trial of the Activity of Seviteronel in Patients With Androgen Receptor (AR)-Positive GBM
Secondary ID [1] 0 0
START
Universal Trial Number (UTN)
Trial acronym
START
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Androgen Receptor Gene Overexpression 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SEVI-D (Seviteronel in combination with dexamthasone)

Experimental: Adrogen Postive Solid Tumours -


Treatment: Drugs: SEVI-D (Seviteronel in combination with dexamthasone)
Use of SEVI-D (Serivteronel and dexamethasone) in the treatment of androgen receptor positive solid tumours.
Serivteronel will be administered orally at 450 mg (3 tables) once daily. It will be given in combination with one oral tablet of 0.5 mg tablet of Dexamethosone. SEVI-D will be continuously administered daily while on the study.
Clinical and safety assessments are scheduled every 4 weeks during the study and then every 8 weeks after the end of the safety follow up period of the study.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective tumour response or the ratio of time-to-progression over the preceding period - Assessing radiological images at each time point using either RECIST 1..1 or RANO criteria for disease progression.
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
Overall survival (OS) - Number of Patients alive >= 5 years
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. - The type and frequency of treatment-related adverse events as assessed by CTCAE v4.03.
Timepoint [2] 0 0
Through study completion, average 1 year
Secondary outcome [3] 0 0
Change in quality of life measurements during treatment - Change from Baseline in EORTC QLQ-C30 v3 questionnaires
Timepoint [3] 0 0
Through study completion, average 1 year
Secondary outcome [4] 0 0
Change in pain score measurements during treatment - Change from Baseline in BP-SF questionnaires
Timepoint [4] 0 0
Through study completion, average 1 year

Eligibility
Key inclusion criteria
1. To be eligible for treatment in the study, patients must continue to meet all of the
inclusion criteria and none of the exclusion criteria at the time of registration.
Male or female patients, aged 18 years and older, with pathologically confirmed
advanced GBM;

2. Sufficient and accessible tissue for molecular screening;

3. Patients receiving their last line of standard treatment or who have received and
failed all standard anticancer therapy (where standard therapy exists) or have
documented unsuitability for any further standard anticancer therapy Poor prognosis
cancers or cancers with low expected response rate to standard treatment (in the
opinion of the investigator and based on available evidence) may be screened on an
earlier line of treatment.

1. Failure is defined as either progression of disease (clinical or radiological) or
intolerance to standard therapy resulting in the discontinuation of the therapy.

2. Documented unsuitability for further standard therapy includes known
hypersensitivity, organ dysfunction or other patient factors that would make
therapy unsuitable in the judgement of the responsible investigator;

4. ECOG performance status 0, 1 or 2;

5. Willing and potentially able to comply with study requirements, including treatment,
timing and/or nature of required assessments; It is the intention to screen patients
who are in principle wishing to take part in the START study if they are found to have
an appropriate tumour biomarker and are still eligible for enrolment at the time of
the treatment phase;

6. Signed, written informed consent to participation in the molecular screening and
treatment study.

7. Received and failed all standard anticancer therapy or have documented unsuitability
for any further standard therapy, if standard therapy exists;

8. Clinical or radiological progression on or following last anticancer therapy;

9. Adequate organ system function as assessed by the following minimal laboratory
requirements (within 7 days prior to first administration of study drug):

1. bone marrow function; platelets = 100 x 109/L, ANC = 1.5 x 109/L, and haemoglobin
=9g/dL (5.6mmol/L); white blood cell count =3,000 cells/µL

2. liver function; ALT/AST = 3 x ULN (in the absence of liver metastases, = 5 x ULN
for patients with liver involvement) and total bilirubin =1.5xULN;

3. renal function; serum creatinine =1.5xULN;

10. Meet any additional inclusion criteria specified in the relevant study addendum;

11. Signed, written informed consent to participation in the specific treatment study.

12. AR-positive GBM confirmed by immunohistochemistry

13. Able to comply with study requirements
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will include those relevant for screening but also include:

1. Suitable for standard therapy or accepted standard care, if the patient has not been
previously treated;

2. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications
which may contraindicate participation and/or interact with seviteronel, dexamethasone
or the GnRH analogue;

3. Other co-morbidities or conditions that may compromise assessment of key outcomes or
in the opinion of the clinician, limit the ability of the patient to comply with the
protocol;

4. For non central nervous system (CNS) cancers, patients with symptomatic CNS
involvement of his/her cancer. Subjects with stable neurological function, on stable
doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS
progression within 12 weeks prior to study entry are eligible;

5. History of another malignancy within 2 years prior to registration unless adequately
treated and determined free of progressive and metastatic disease for at least 6
months. Patients with a past history of adequately treated carcinoma-in-situ, basal
cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial
transitional cell carcinoma of the bladder are eligible;

6. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal,
infertile, or use a reliable means of contraception. Women of childbearing potential
must have a negative pregnancy test done within 7 days prior to registration. Men must
have been surgically sterilised or use a barrier method of contraception (double
barrier, if required).

7. Known history of hypersensitivity to active or inactive components of seviteronel,
dexamethasone, and/or GnRH analoge;

8. Previous treatment with seviteronel or same class of agent;

9. Treatment with any of the following anti-cancer therapies prior to the first dose of
study treatment:

- Radiation therapy, surgery or tumour embolization within 14 days prior to the
first dose of study treatment. Palliative radiotherapy (for analgesia) is
acceptable only if the irradiated field does not include target lesions;

- Immunotherapy within 28 days prior to the first dose of study treatment;

- Chemotherapy, biologic therapy, or hormonal therapy within 14 days or 5
half-lives of a drug prior to the first dose of study treatment or until recovery
from previous therapy (whichever is longer);

10. Administration of any investigational treatment within 30 days or 5 half-lives
(whichever is longer) prior to receiving the first dose of study treatment;

11. Active prostate cancer requiring treatment.

12. Active breast cancer requiring treatment.

13. Symptomatic central nervous system cancer. Subjects with stable neurological function,
on stable doses of steroids/anti-epileptics over 4 weeks prior to screening are
eligible.

14. Corrected QT interval by the Fridericia correction formula (QTcF) on the screening
electrocardiogram (ECG) >470 msec. If the screening ECG QTcF interval is >470 msec, it
may be repeated once, and if the repeat ECG is <470 msec, the patient may be enrolled.

15. Clinically significant cardiac arrhythmias (eg, ventricular tachycardia, ventricular
fibrillation, torsades de pointes, second degree or third degree atrioventricular
heart block without a permanent pacemaker in place).

16. Any medical condition that could preclude patient participation in the study, pose an
undue medical hazard, or which could interfere with study results.

17. Class III or IV Congestive Heart Failure as defined by the New York Heart Association
functional classification system within the previous 6 months.

18. Known active Human Immunodeficiency Virus, Hepatitis B, or Hepatitis C infections.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst

Funding & Sponsors
Primary sponsor type
Other
Name
St Vincent's Hospital, Sydney
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study's purpose is to facilitate and expedite the clinical testing of SEVI-D in a
population with advanced GBM that are androgen receptor (AR) positive.

Who is it for? You may be eligible for this study if you have a GBM with
clinical/radiological progression on or following last anticancer therapy.

Study details:

All participants will be screened to confirm if their GBM is AR positive by the study team.
If eligible, participants will receive the medications of Serivteronel and Dexamethasone
(also known as SEVI-D) by oral tablets continuously per cycle (4 weeks). Participants will be
asked to have blood tests, scans, complete questionnaire and regularly meet with the study
doctor and team.

It is hoped this research will demonstrate this treatment could be beneficial for the
treatment of GBM that are known to be human androgen receptor positive.
Trial website
https://clinicaltrials.gov/show/NCT03600467
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Robert Kent
Address 0 0
Country 0 0
Phone 0 0
+61 2 9355 5611
Fax 0 0
Email 0 0
SVHS.CancerResearch@svha.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03600467