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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04947189




Registration number
NCT04947189
Ethics application status
Date submitted
25/03/2021
Date registered
1/07/2021
Date last updated
16/10/2023

Titles & IDs
Public title
Seviteronel in Combination With Chemotherapy in Androgen-receptor Positive Metastatic Triple-negative Breast Cancer
Scientific title
4CAST: A Phase 1b Dose Exploration and Dose Expansion, Open-label, Single-centre Study Evaluating the Safety and Efficacy of INO-464 in Combination With Chemotherapy in Patients With metASTatic Breast Cancer
Secondary ID [1] 0 0
4CAST
Universal Trial Number (UTN)
Trial acronym
4CAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

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

Experimental: Seviteronel, dexamethasone and docetaxel - Part 1: Seviteronel will be administered orally beginning with 450 mg (3 x 150 mg tablets) once daily along with 0.5 mg dexamethasone, continuously in 28-day cycles with docetaxel 75mg/m2 administered intravenously 3 weekly.
Part 2: The recommended phase 2 dose for seviteronel (established in Part 1) once daily along with 0.5 mg dexamethasone, continuously in 21-day cycles with docetaxel 75mg/m2 administered intravenously 3 weekly.


Treatment: Drugs: Seviteronel-D (Seivteronel in combination with dexamethasone)
Use of Seviteronel-D (Serivteronel and dexamethasone) in the treatment of androgen receptor positive solid tumours.

Treatment: Drugs: Docetaxel
Use of docetaxel chemotherapy for solid tumours
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended phase 2 dose of seviteronel plus dexamethasone and docetaxel
Timepoint [1] 0 0
10 weeks
Secondary outcome [1] 0 0
Number of patients with treatment-related adverse events
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Overall response rate (ORR)
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Duration of response (DoR)
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
2 years

Eligibility
Key inclusion criteria
- Signed written and voluntary informed consent.

- Patient must be willing and able to comply with scheduled visits, treatment plan,
laboratory tests and other study procedures.

- Age 18 years or older male or female.

- Eastern Cooperative Oncology Group Performance Status of 0 or 1

- At least 4 weeks washout period from previous line of treatment, 2 weeks from
radiotherapy

- Adequate haematologic and organ function within 14 days before the first study
treatment on cycle1, day 1

- Life expectancy of at least 3 months

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per
year during the treatment period and for at least 28 days after the last dose of
seviteronel or, 6 months after the last dose of chemotherapy whichever occurs later.

- Part 1: Histological or cytological-based diagnosis of breast cancer. Any of the three
major subtypes of breast cancer is permitted for the phase 1b study, i.e., hormone
receptor positive breast cancer i.e. oestrogen and/or progesterone positive in greater
than 1% of cells by immunohistochemistry (IHC), or human epidermal growth factor
receptor (HER2) positive breast cancer, i.e., IHC 3+ or in situ hybridisation (ISH)
positive according to standard ASCO/CAP guidelines or triple-negative breast cancer,
i.e., HER2-negative by ASCO/GAO Guidelines and <1% expression of estrogen and/or
progesterone receptor by IHC.

- Part 2: Histological or cytological-based diagnosis of triple-negative breast cancer.
The tumor must be HER2-negative by ASCO/GAO Guidelines and <1% expression of estrogen
and /or progesterone receptor by IHC.

o The tumor must also show androgen receptor positivity (i.e., AR>0%) by IHC or gene
classifier (molecular testing).

- Measurability of lesion: have at least 1 measurable lesion assessable using standard
techniques by RECIST v1.1

- Patients must have advanced or recurrent breast cancer pre-inclusion number 8, for
whom docetaxel is considered an appropriate treatment option.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Inability to comply with study and follow-up procedures.

- History of malabsorption syndrome or other condition that would interfere with enteral
absorption or results in the inability or unwillingness to swallow pills.

- Active infection requiring antibiotics.

- Other invasive malignancy within 2 years except for malignancies determined to have
low recurrence potential in discussion with study PI.

- Known active tuberculosis.

- Female patients who are pregnant or breast-feeding.

- Male or female patients of reproductive potential who are not willing to use effective
birth control from screening to 90 days post treatment.

- Women of childbearing potential (who are not postmenopausal within 12 months of
non-therapy induced amenorrhea, nor surgically sterile) must have a negative serum
pregnancy test result within 3 days prior to initiation of study treatment.

- Uncontrolled intercurrent illness, including psychiatric illness/social situations
that would limit compliance with study requirement, substantially increase risk of
incurring adverse events, or compromise the ability of the subject to give written
informed consent.

- History or current evidence of HIV infection.

- Known clinically significant history of liver disease consistent with Child-Pugh Class
B or C, including active viral or other hepatitis (e.g., positive for hepatitis B
surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current
drug or alcohol abuse, or cirrhosis:

- Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as having a negative HBsAg test and a positive antibody to hepatitis B core
antigen antibody test) are eligible.

- Patients positive for HCV antibody are eligible only if polymerase chain reaction is
negative for HCV RNA.

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure
during the course of the study

- Placement of a vascular access device is not considered major surgery.

- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that, in the investigator's opinion, gives reasonable suspicion of
a disease or condition that contraindicates the use of an investigational drug or that
may affect the interpretation of the results or render the patient at high risk from
treatment complications

- Patients with symptomatic central nervous system (CNS) metastasis and/or carcinomatous
meningitis. Patients with treated CNS metastases are eligible for this study if they
are not receiving corticosteroids and/or anticonvulsants for at least 7 days prior to
first dose of study treatment, and their disease is asymptomatic and radiographically
stable for at least 30 days prior to consent by repeat imaging (repeat imaging should
be performed during study screening).

- Unresolved, clinically significant toxicity NCI CTCAE v5.0 grade 2 or higher, from
prior therapy, except for alopecia, endocrinopathy on stable hormonal replacement, and
others as approved by study PI.

- Patients who have received palliative radiation treatment to peripheral sites (e.g.,
bone metastases) for pain control and whose last treatment was completed 14 days prior
to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all
acute, reversible effects.

- Uncontrolled pleural effusion, pericardial effusion, or ascites.

- Known hypersensitivity or contraindication to any component of the study treatment.

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

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 1/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
1/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
65
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre - 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
To facilitate the clinical testing of seviteronel and dexamethasone (SEVI-D) in combination
with docetaxel in androgen receptor (AR) positive triple-negative breast cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04947189
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
Rachel F Dear, PhD
Address 0 0
Country 0 0
Phone 0 0
+61293553633
Fax 0 0
Email 0 0
rachel.dear@svha.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04947189