Clinical trial NCT01969578: Androgen Deprivation Therapy in Advanced Salivary Gland Cancer
Official title: A Randomized Phase II Study to Evaluate the Efficacy and Safety of Chemotherapy (CT) vs Androgen Deprivation Therapy (ADT) in Patients With Recurrent and/or Metastatic, Androgen Receptor (AR) Expressing, Salivary Gland Cancer (SGCs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Salivary Gland Cancer
Keywords: salivary duct cancer
adenocarcinoma, NOS
androgen deprivation
androgen receptor
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2013-10-25
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Salivary Gland (SG) Cancers are a rare and heterogeneous group of tumors, usually approached by multidisciplinary teams in high specialized centers. Until today no standard of care exists to treat these cancers. The identification of a target, the androgen receptor, in SG tumors has allowed for new treatment strategies options for this rare group of diseases. As a matter of fact, strong positivity for androgen expression has been found in salivary duct carcinoma and adenocarcinomas. The purpose of this study is therefore to evaluate the efficacy and safety of chemotherapy versus androgen deprivation therapy (ADT) in patients with recurrent and/or metastatic AR expressing SGCs.

The study will include two cohorts of patients: Cohort A, which comprises chemo-naïve patients, and Cohort B, which comprises pretreated patients.

Detailed description: Patients in Cohort A will be randomized 1:1 at the study entry to receive ADT (triptorelin + bicalutamide 50 mg) or standard chemotherapy. Patients of Cohort A randomized to the control arm (chemotherapy arm) will be given the option to enter Cohort B at the time of disease progression. As long as Cohort A is open to recruitment, patients who will be treated by chemotherapy will be simultaneously enrolled in Cohort B. Accrual in Cohort B will be stopped when recruitment of 76 eligible patients in Cohort A is reached.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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;
* 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;
* 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
* history of allergic reactions attributed to compounds of similar chemical or biological composition to cis/carboplatin, paclitaxel, doxorubicin, bicalutamide or triptorelin;
* concomitant medications with terfenadine, astemizole, cisaprid
* use of phenytoin
* Patients who received vaccine for yellow fever
* active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix;
* positive serum pregnancy test within 1 week prior to the first dose of study treatment for Women of child bearing potential (WOCBP);
* 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.
* 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;
* written informed consent not given according to ICH/GCP, and national/local regulations, before patient registration
* 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).

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 37 months after First Patient In
measure: Response rate (RR)
timeFrame: 37 months after First Patient In
Secondary outcomes:
measure: Response Rate (RR)
timeFrame: 37 months after First Patient In
measure: Progression Free Survival (PFS)
timeFrame: 37 months after First Patient In
Other outcomes:
measure: Overall Survival (OS)
timeFrame: 37 months after First Patient In
measure: Adverse Events according to CTCAE v4.0
timeFrame: 37 months after First Patient In
Locations:
city: Vienna
country: Austria
facility: Medical University Vienna - General Hospital AKH
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Nantes
country: France
facility: Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris - Hopital Tenon
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole - Institut Claudius Regaud
city: Vandoeuvre-Les-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Jena
country: Germany
facility: Universitaetsklinikum Jena-Radiation Therapy and Radiooncology Clinic
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden
city: Athens
country: Greece
facility: Athens University - Attikon University General Hospital
city: Budapest
country: Hungary
facility: National Institute Of Oncology
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Trento
country: Italy
facility: Azienda Provinciale per i Servizi Sanitari - Ospedale Santa Chiara
city: Amsterdam
country: Netherlands
facility: Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center Nijmegen
Study officials:
affiliation: Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
name: Lisa Licitra
role: PRINCIPAL_INVESTIGATOR
affiliation: The Royal Marsden
name: Kevin Harrington
role: STUDY_CHAIR
References: