Seviteronel in Combination With Chemotherapy in Androgen-receptor Positive Metastatic Triple-negative Breast Cancer

NCT04947189 | Recruiting Phase 1 DMC

• 1 other identifier: 4CAST
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Triple Negative Breast Cancer

Keywords

Androgen receptor positive

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose of seviteronel plus dexamethasone and docetaxel

  A patient will be considered evaluable for dose limiting toxicity (DLT) if they have completed two cycles of docetaxel in an 8-week period with at least 80% of the planned INO-464 dose. Toxicity will be graded using CTCAE version 5.0

  10 weeks

Secondary Outcomes (4)

• Number of patients with treatment-related adverse events

  2 years

• Overall response rate (ORR)

  2 years

• Duration of response (DoR)

  2 years

• Overall survival (OS)

  2 years

Other Outcomes (3)

• Gene expression signatures in tumour biopsies treated with seviteronel

  2 years

• Androgen receptor protein signature in biopsies treated with seviteronel

  2 years

• Biomarker expression in blood and/or tumor tissue following seviteronel treatment

  2 years

Study Arms (1)

Seviteronel, dexamethasone and docetaxel

EXPERIMENTAL

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.

Drug: Seviteronel-D (Seivteronel in combination with dexamethasone); Drug: Docetaxel

Interventions

Seviteronel-D (Seivteronel in combination with dexamethasone) DRUG

Use of Seviteronel-D (Serivteronel and dexamethasone) in the treatment of androgen receptor positive solid tumours.

Also known as: INO-464

Seviteronel, dexamethasone and docetaxel

Docetaxel DRUG

Use of docetaxel chemotherapy for solid tumours

Seviteronel, dexamethasone and docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St Vincent's Hospital, Sydney: lead

Study Sites (1)

Kinghorn Cancer Centre

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Dexamethasone; seviteronel; Docetaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Rachel F Dear, PhD

CONTACT

+61293553633; rachel.dear@svha.org.au

Christine Chaffer, PhD

CONTACT

+61293555824; c.chaffer@garvan.org.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Anthony Joshua

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: July 1, 2021
• Study Start: November 1, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

AU (1)