Androgen Deprivation Therapy in Advanced Salivary Gland Cancer

Prior treatment

• Actively bleeding tumor if the patient is intended to be treated with carboplatin
• Patients with bone disease or brain disease as the sole disease site; brain metastases are allowed in case of systemic disease, but must have been treated at least 4 weeks before enrollment and must be stable after that;
• previous cardiac toxicity induced by another anthracycline or previous exposure to maximum cumulative dose of another anthracycline if the patient is intended to be treated with doxorubicin
• concomitant medications with terfenadine, astemizole, cisaprid
• Patients who received vaccine for yellow fever
• participation in another interventional clinical trial in the preceding 4 weeks prior to randomization
• for cohort A patients: previous chemotherapy for recurrent/metastatic disease (previous chemotherapy given concomitantly with RT in the past is allowed, including cisplatin but it should be completed at least 6 months before enrollment).

Other illness

• history of allergic reactions attributed to compounds of similar chemical or biological composition to cis/carboplatin, paclitaxel, doxorubicin, bicalutamide or triptorelin;
• active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix;
• psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;

Lab values

• recent history of congestive heart failure, unstable angina within the past 3 months, cardiac arrhythmia, myocardial infarction, congenital long QTc prolongation, stroke, TIA within the past 6 months;
• positive serum pregnancy test within 1 week prior to the first dose of study treatment for Women of child bearing potential (WOCBP);

Other

• use of phenytoin
• no adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment for patients of childbearing / reproductive potential.
• written informed consent not given according to ICH/GCP, and national/local regulations, before patient registration

• Histologically proven diagnosis of recurrent and/or metastatic salivary duct cancer; adenocarcinoma, NOS; and AR expression in at least 70% of nuclei of neoplastic cells based on central review
• Sufficient tissue must be available either historically or a biopsy must be done as a part of this study and sent to central review for patients enrolled in both cohorts
• Presence of at least one uni-dimensional measurable lesion by CT-scan or MRI according to RECIST criteria version 1.1 (target lesion).
• Patients older than 18 years old;
• Performance Status ECOG 0-1;
• Adequate bone marrow function:
• WBC ≥ 3.5/10exp9L
• absolute neutrophil count ≥ 1,5x10exp9/L
• hemoglobin \> 9 g/dL
• platelet count ≥ 100x10exp9/L
• Adequate liver function:
• AST \< 2.5 times upper limit of normal
• ALT \< 2.5 times upper limit of normal
• bilirubin \< 1.5 times upper limit of normal
• the concomitant evidence of AST \< 2.5 times upper limit of normal, ALT \< 2.5 times upper limit of normal and bilirubin \> 1.5 times upper limit of normal is not allowed
• Adequate renal function:
• serum creatinine level (≤ 1.3 mg/dL)
• calculated creatinine clearance ≥ 60 mL/min based on the standard Cockcroft and Gault formula
• Adequate cardiac function as demonstrated by a clinically normal 12 lead ECG; additionally for patients who will receive Cisplatin and Doxorubicin adequate cardiac function should be demonstrated by a left ventricular ejection fraction (LVEF) ≥ 50% (within 2 weeks prior to treatment start)