Activity of Seviteronel in Patients With Androgen Receptor (AR)-Positive Glioblastoma — START  

Solid Tumor Clinical Trial

Official title: A Single-arm, Open-label, Signal-seeking, Phase IIa Trial of the Activity of Seviteronel in Patients With Androgen Receptor (AR)-Positive GBM

Status Terminated

Clinical Trial 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.

Clinical Trial Description

Background:

The human androgen receptor (AR) is a steroid hormone receptor that is expressed in multiple reproductive tissues and has important effects on multiple organ systems. The AR is a major target for the treatment of prostate cancer, and, more recently, for treatment of breast cancer. However, the AR is also expressed on many other tissues and plays vital roles in other cancer types, such as head and neck cancers (eg, salivary gland and thyroid cancers), cutaneous malignancies (eg, melanoma and basal cell carcinoma), sarcomas, and genitourinary cancers (eg, renal and bladder cancers). There are very few studies investigating AR-targeted therapies for indications other than prostate or breast cancer; however the few anecdotal reports and small studies that have been performed suggest that AR-positive tumours may respond to therapy with AR-targeted agents. In this study we are concentrating on GBM Seviteronel is a dual selective P450C17,20-lyase (CYP17 lyase) and AR inhibitor currently being investigated in Phase 1/2 trials for prostate and breast cancers. Seviteronel has shown promising preclinical activity in some breast cancer models, and seviteronel in combination with dexamethasone (SEVI-D) has shown promising preliminary activity for treatment of metastatic castration-resistant prostate cancer. Therefore, SEVI-D could be beneficial for the treatment of other cancers that are known to be AR-positive such as GBM

Aim:

The overall aim is to facilitate and expedite the clinical testing of rational therapeutic hypotheses in a population with advanced cancer and unmet need, with a particular, but not exclusive, focus on rare or neglected cancers. The program will evaluate the clinical activity of SEVI-D in subjects with AR-positive GBM

Primary Objective:

To test the clinical activity of novel targeted treatments and/or indications as measured by objective tumour response or the ratio of time-to-progression on study over the preceding period

Secondary Objectives:

1. Overall survival (OS) (death from any cause);

2. Safety and tolerability of treatment (rates of adverse events)

3. Health related quality of life during treatment (EORTC QLQ-C30v.3 questionnaire or brief pain inventory, if applicable).

4. To evaluate the feasibility, efficiency and utility of an overarching framework protocol for multiple, parallel signal-seeking clinical substudies;

5. To evaluate a mechanism for screening patients for actionable biomarkers to be used to guide therapy.

Population:

Patients with AR-positive GBM as confirmed by immunohistochemistry.

Treatments:

Seviteronel, will be administered orally at 450 mg (3 x 150 mg tablets) for men with 0.5 mg dexamethasone (tablet) once daily plus a GnRH analogue (depot injection). Seviteronel, will be administered orally at 450 mg (3 x 150 mg tablets) for post menopausal women, once daily in combination with once daily 0.5 mg dexamethasone (tablet). For premenopausal women (with intact ovaries), a GnRH analogue (depot injection) will also need to be admistered. See Treatment Study Table below. Patients will take seviteronel and dexamethasone each day continuously in 28-day cycles.

Assessments:

Screening for participation in the screening platform includes the review of patient history, current health status, availability of a biospecimen for AR screening and patient willingness to be in a trial if eligible.

Clinical and safety assessments are scheduled prior to registration and then every 8 weeks until death.

Imaging and other response assessments are required at baseline and 8-weekly from cycle 1 day 1 until progression.

Blood collection for translational studies will occur at:

1. Baseline (collected within 21 days prior to registration) or within 28 days of C1D1 treatment

2. Every 2nd cycle

3. At End of treatment ;

Related Conditions & MeSH terms

• Androgen Receptor Gene Overexpression
• Solid Tumor

• NCT number: NCT03600467
• Study type: Interventional
• Source: St Vincent's Hospital, Sydney
• Status: Terminated
• Phase: Phase 2
• Start date: August 13, 2018
• Completion date: February 28, 2021