pre-treated post-menopausal patients with ER/PgR-negative/AR-positive or ER and/or PgR-positive/AR-positive metastatic breast cancer MedDRA version: 15.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: LETROZOLE
Product Code: LETROZOLE
Pharmaceutical Form: Tablet
INN or Proposed INN: LETROZOLE
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concent
Sponsors
IRCCS ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with metastatic breast cancer 2. AR receptor positivity of primary tumor cells or tumor cells of a metastatic site is required 3. primary tumor cells or tumor cells of a metastatic site imust be HER2 negative 4. Patients must have measurable disease 5. In case of ER-positive disease, previous endocrine treatment in adjuvant or metastatic setting is required and patients must be resistant to aromatase inhibitors. In particular DHEA will be administered in combination with the same aromatase inhibitor during which the progression of disease was found 6. No more than 2 previous lines of chemotherapy for ER-pos tumors and not more than 3 lines of chemotherapy for ER-neg tumors are allowed 7. Women must be in post-menopausal status 8. Life expectancy must be of greater of 12 weeks Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. AR-receptor negativity of primary tumor cells or tumor cells of a metastatic site. AR is reported as negative if less than 10% of cells immunostained in a tumor. 2. HER2 positivity of primary tumor cells or tumor cells of a metastatic site 3. Physician opinion of a too rapid disease progression (like disease widespread in visceral organs like liver or lung in few months) that could suggest the physician a more benefit from chemotherapy treatment even if elegibility criteria for enrollment are satisfied 4. Chemotherapy administration within 3 weeks prior to start of protocol therapy or not recovered from adverse events due to agents administered more than 3 weeks earlier 5. Brain metastasis not treated or in progression requiring treatment (radiotherapy, surgery or high dose steroidal and antiedemigen treatment) in the 2 weeks prior to start of protocol therapy. Patients with brain metastasis as unique site of metastasis are excluded 6. Have received supplement of estrogen or progesterone within 4 weeks prioir to study enter 7. Major surgery during the 21 days before before starting of protocol therapy or planned during the study treatment. 8. Other detectable malignant neoplastic diseases (even a second primitive breast cancer) in the patient’s medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma of the skin and in situ carcinoma of the uterine cervix); 9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 10. Participation in another clinical trial with any investigational agents within 3 weeks prior to study screening. 11. Previous treatment with androgens or DHEA. Previous treatment with AI is required in case of ER+ and/or PgR positive tumors 12. History of allergic reactions attributed to compounds of similar chemical or biologic composition to DHEA or AI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 3 years;Main Objective: • Safety of treatment of the combination of DHEA and an aromatase inhibitor (anastrozole or letrozole or exemestane) in pre-treated post-menopausal metastatic breast cancer patients • Efficacy (evaluated as clinical benefit) of treatment of the combination of DHEA and an aromatase inhibitor (anastrozole or letrozole or exemestane) in pre-treated post-menopausal metastatic breast cancer patients ;Secondary Objective: • To assess quality of life (QOL) of patients • To evaluate time-to-event endpoints (TTP, OS, DOR). For the biological part, we will evaluate: 1) Correlation between AR expression and clinical and biological features 2) Evaluation of AR expression on primitive and/or metastatic site in the two distinct populations of patients: ER/PgR- neg/AR-pos and ER-pos and/or PgR-pos/AR-pos 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 CTCs evaluated at baseline before study treatment and at the moment of discontinuation of treatment. 6) Measurement of serum glucuronidated DHEA metabolites concentration at baseline before study treatment and at the moment of discontinuation of treatment ;Primary end point(s): • Safety of treatment of the combination of DHEA and an aromatase inhibitor (anastrozole or letrozole or exemestane) in pre-treated post-menopausal metastatic breast cancer patients • Efficacy (evaluated as clinical benefit) of treatment of the combination of DHEA and an aromatase inhibitor (anastrozole or letrozole or exemestane) in pre-treated post-menopausal metastatic breast cancer patients The first 6 enrolled patients will be closely controlled for safety (at day 14 and 28 of the cycle 1 and 2, assessi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To assess quality of life (QOL) of patients • To evaluate time-to-event endpoints (TTP, OS, DOR). 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/AR-positive 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. 6) Measurement of serum glucuronidated DHEA metabolites [as androsterone (ADT)-G, 3alpha (a)-diol-G, estrone (E1)-G and estradiol (E2)-G] concentration at baseline before study treatment and at the moment of discontinuation of treatment.;Timepoint(s) of evaluation of this end point: 3 years | — |
Countries
Italy
Contacts
Public Contactdata manager
IRCCS IRST
Outcome results
None listed