Clinical Trial: 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)
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
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 o
Brief 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:
- Correlation between AR expression and clinical and biological features (tumor size, nodal status, histotype, grading, proliferative index, ER, PgR, HER2)
- 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
- 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.
- CTCs ana
Detailed 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:
- Correlation between AR expression and clinical and biological features (tumor size, nodal status, histotype, grading, proliferative index, ER, PgR, HER2)
- 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
- 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.
- CTCs ana
Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Current Primary Outcome: Clinical benefit rate (CB) [ Time Frame: 36 months ]
the proportion of patients with stability, partial response and complete response of the disease after 4 months of therapy.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Time to tumor progression (TTP) [ Time Frame: 36 months ]It is defined as the time from randomization until objective tumor progression NOT including death.
- Duration of response (DOR) [ Time Frame: 36 months ]The time from the date of response documentation to the date of disease progression documentation.
- Overall survival (OS) [ Time Frame: 36 months ]The time from the date of randomization to date of death from any cause.
- Quality of life Quality of life Quality of life Quality of life [ Time Frame: 36 months ]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.
- Correlation between AR expression and clinical and biological features [ Time Frame: 36 months ]
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.
- 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) [ Time Frame: 36 months ]
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.
- Evaluation of ER, PgR, HER2 expression on tumor cells of metastatic sites (when it is possible) and comparison with the same features of the the primary site. [ Time Frame: 36 months ]
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.
- Circulating Tumor Cells (CTCs) analysis [Optionally, only for patients enrolled at IRCCS IRST of Meldola and who signed additional informed consent ] [ Time Frame: 36 months ]Analyzing 15-20 ml peripheral blood (PB). The blood collection will be taken before starting treatment at baseline and at the end of treatment.
- Safety [ Time Frame: 36 months ]Assessed by collecting adverse events (AE) and serious adverse events (SAE) during the course of the study.
Original Secondary Outcome: Same as current
Information By: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Dates:
Date Received: November 21, 2013
Date Started: March 2013
Date Completion:
Last Updated: September 28, 2016
Last Verified: September 2016
- Time to tumor progression (TTP) [ Time Frame: 36 months ]
