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) — ARTT  

Estrogen Receptor Positive Breast Cancer Clinical Trial

Official title: 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)

Status Terminated

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Androgen Receptor Gene Overexpression
• Breast Neoplasms
• Estrogen Receptor Negative Neoplasm
• Estrogen Receptor Positive Breast Cancer
• Metastatic Breastcancer
• Neoplasms
• Progesterone Receptor Negative Neoplasm
• Progesterone Receptor Positive Tumor

• NCT number: NCT02000375
• Study type: Interventional
• Source: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Status: Terminated
• Phase: Phase 2
• Start date: March 2013
• Completion date: February 2016