Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Menopause

Kennedy Disease

All Drugs and Chemicals

Antineoplastic Agents

Other Dietary Supplements

Androgens

Exemestane

Letrozole

Anastrozole

Dehydroepiandrosterone

Adjuvants, Immunologic

Immunologic Factors

DHEA (Dehydroepiandrosterone)

Daily oral administration of DHEA at the dosage of 100 mg/die in combination with a daily oral administration of anastrozole at dosage of 1 mg/die or letrozole at the dosage of 2.5 mg/die or exemestane at the dosage of 25 mg/die without interruption.

DHEA: Daily oral administration of DHEA(Dehydroepiandrosterone) at the dosage of 100 mg/die in combination with a daily oral administration of anastrozole at dosage of 1 mg/die or letrozole at the dosage of 2.5 mg/die or exemestane at the dosage of 25 mg/die without interruption.

DHEA

Elisabetta Pietri, MD

A phase II non randomized study evaluating the role of Androgen Receptors as Targets for therapy of pre-treated postmenopausal patients with ER/PgR-negative/AR-positive or ER and/or PgR-positive/AR-positive metastatic breast cancer.

Study Design: Multicentric, Open-label not randomized trial.

Description of Study Treatment:

Daily oral administration of DHEA (Dehydroepiandrosterone) at the dosage of 100 mg/die in combination with a daily oral administration of anastrozole at dosage of 1 mg/die or letrozole at the dosage of 2.5 mg/die or exemestane at the dosage of 25 mg/die without interruption until discontinuation for progression of disease, unacceptable toxicity or discontinuation/withdrawal of participants from study treatment.

Number of Subjects:

12 patients per group in the first step; if the number of responders is greater or equal to 2, recruitment will continue up to a total of 35 patients (per group).

For the biological part, we will evaluate:

1. Correlation between AR expression and clinical and biological features (tumor size, nodal status, histotype, grading, proliferative index, ER, PgR, HER2)
2. Evaluation of AR expression on primitive and/or metastatic site in the two distinct populations of patients: ER/PgR- negative/ARpositive and ER-positive and/or PgR-positive/AR-positive
3. Evaluation of ER, PgR, HER2 expression on tumor cells of metastatic site (when it is possible) and comparison with the same features of primitive tumor.
4. CTCs analysis in term of molecular characteristics (gene expression and mutations) and functionality (vitality and tumorigenicity).
5. Prognostic and predictive role of Circulating Tumor Cells (CTC) evaluated at baseline before study treatment and at the moment of discontinuation of treatment.

A phase II non randomized study evaluating the role of Androgen Receptors as Targets for therapy of pre-treated postmenopausal patients with ER/PgR-negative/AR-positive or ER and/or PgR-positive/AR-positive metastatic breast cancer.

Study Design: Multicentric, Open-label not randomized trial.

Description of Study Treatment:

Daily oral administration of DHEA (Dehydroepiandrosterone) at the dosage of 100 mg/die in combination with a daily oral administration of anastrozole at dosage of 1 mg/die or letrozole at the dosage of 2.5 mg/die or exemestane at the dosage of 25 mg/die without interruption until discontinuation for progression of disease, unacceptable toxicity or discontinuation/withdrawal of participants from study treatment.

Number of Subjects:

12 patients per group in the first step; if the number of responders is greater or equal to 2, recruitment will continue up to a total of 35 patients (per group).

For the biological part, we will evaluate:

1. Correlation between AR expression and clinical and biological features (tumor size, nodal status, histotype, grading, proliferative index, ER, PgR, HER2)
2. Evaluation of AR expression on primitive and/or metastatic site in the two distinct populations of patients: ER/PgR- negative/ARpositive and ER-positive and/or PgR-positive/AR-positive
3. Evaluation of ER, PgR, HER2 expression on tumor cells of metastatic site (when it is possible) and comparison with the same features of primitive tumor.
4. CTCs analysis in term of molecular characteristics (gene expression and mutations) and functionality (vitality and tumorigenicity).
5. Prognostic and predictive role of Circulating Tumor Cells (CTC) evaluated at baseline before study treatment and at the moment of discontinuation of treatment.

Statistical Considerations:

The sample size required for each treatment arm will be predicted using a SIMON two-stage design with a 10 percent alpha and beta error.

Assuming an acceptable minimum clinical benefit P0 equal to 10 percent and an auspicious clinical benefit P1 equal to 30 percent, we plan to recruit 12 patients per group in the first step.

If the number of responders is greater or equal to 2, recruitment will continue up to a total of 35 patients (per group).

If the number of responders is greater or equal to 6, the combination will be considered active and worthy of further evaluation.

If a subgroup population is discontinued at the end of the first step, the study will be continued with the other subgroup.

A Phase II Study Evaluating the Role of Androgen Receptors as Targets for Therapy of Pre-treated Post-menopausal Patients With ER/PgR-negative/AR-positive or ER and/or PgRpositive/ AR-positive Metastatic Breast Cancer (ARTT)

A Phase II Non Randomized Study Evaluating the Role of Androgen Receptors as Targets for Therapy of Pre-treated Post-menopausal Patients With ER/PgR-negative/AR-positive or ER and/or PgRpositive/ AR-positive Metastatic Breast Cancer (ARTT)

the proportion of patients with stability, partial response and complete response of the disease after 4 months of therapy.

It is defined as the time from randomization until objective tumor progression NOT including death.

The time from the date of response documentation to the date of disease progression documentation.

The time from the date of randomization to date of death from any cause.

FACT ( Functional Assessment of Cancer Therapy ) -B : a 36-item compilation, subdivided into four primary QOL (Quality of life) domains and a disease specific domain - additional concerns for breast cancer.

Immunohistochemistry for steroid receptors. Antigen expression is evaluated at light microscope (x 200) by two independent observers.

The positivity is expressed as the percentage ratio between immunoreactive and total number of tumor cells. The cut off value \> 10%for AR will be adopted.

Analyzing 15-20 ml peripheral blood (PB). The blood collection will be taken before starting treatment at baseline and at the end of treatment.

Assessed by collecting adverse events (AE) and serious adverse events (SAE) during the course of the study.

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Glioblastoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

Seviteronel

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

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.

SEVI-D (Seviteronel in combination with dexamthasone)

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.

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

START is an open-label, single-arm, multicentre Phase IIa signal-seeking trial.

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

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

Assessing radiological images at each time point using either RECIST 1..1 or RANO criteria for disease progression.

The type and frequency of treatment-related adverse events as assessed by CTCAE v4.03.

Change from Baseline in EORTC QLQ-C30 v3 questionnaires

Change from Baseline in BP-SF questionnaires

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase II Study Evaluating the Role of Androgen Receptors as Targets for Therapy of Pre-treated Post-menopausal Patients With ER/PgR-negative/AR-positive or ER and/or PgRpositive/ AR-positive Metastatic Breast Cancer (ARTT)	NCT02000375	Metastatic Brea... Estrogen Recept... Estrogen Recept... Progesterone Re... Progesterone Re... Androgen Recept...	DHEA	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
A Phase II Study Evaluating the Role of Androgen Receptors as Targets for Therapy of Pre-treated Post-menopausal Patients With ER/PgR-negative/AR-positive or ER and/or PgRpositive/ AR-positive Metastatic Breast Cancer (ARTT)	NCT02000375	Metastatic Brea... Estrogen Recept... Estrogen Recept... Progesterone Re... Progesterone Re... Androgen Recept...	DHEA	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Activity of Seviteronel in Patients With Androgen Receptor (AR)-Positive Glioblastoma	NCT03600467	Solid Tumor Androgen Recept...	SEVI-D (Seviter...	18 Years -	St Vincent's Hospital, Sydney

Spots Global Cancer Trial Database for androgen receptor gene overexpression