Androgen Deprivation Therapy in Advanced Salivary Gland Cancer

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Salivary Gland Cancer
• Intervention / Treatment: Drug: Cisplatin + Doxorubicin; Drug: Carboplatin + Paclitaxel; Drug: bicalutamide + triptorelin

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.

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna - General Hospital AKH
• Belgium
  • Antwerp, Belgium, 2020
    • ZNA Middelheim
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium, 1000
    • Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Leuven, Belgium
    • U.Z. Leuven - Campus Gasthuisberg
• France
  • Bordeaux, France, 33075
    • CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
  • Montpellier, France
    • Institut régional du Cancer Montpellier
  • Nantes, France
    • CHU de Nantes - Hotel Dieu
  • Nantes, France, 44805
    • Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75020
    • Assistance Publique - Hopitaux de Paris - Hopital Tenon
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole - Institut Claudius Regaud
  • Vandoeuvre-Les-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine
  • Villejuif, France
    • Gustave Roussy
• Germany
  • Berlin, Germany, 12200
    • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Jena, Germany, 07747
    • Universitaetsklinikum Jena-Radiation Therapy and Radiooncology Clinic
  • Leipzig, Germany
    • Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden
• Greece
  • Athens, Greece, 12462
    • Athens University - Attikon University General Hospital
• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncology
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Trento, Italy, 38100
    • Azienda Provinciale per i Servizi Sanitari - Ospedale Santa Chiara
• Netherlands
  • Amsterdam, Netherlands, 1007MB
    • Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen (UMCG)
  • Nijmegen, Netherlands
    • Radboud University Medical Center Nijmegen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemotherapy; Chemotherapy = either Cisplatin + Doxorubicin or Carboplatin + Paclitaxel Patients from cohort A (chemonaïve) may be randomized in this arm to receive chemotherapy	Drug: Cisplatin + Doxorubicin; Drug: Carboplatin + Paclitaxel
Experimental: Androgen Deprivation Therapy (ADT); ADT = bicalutamide + triptorelin Patients from cohort A (chemonaive) may be randomized to receive ADT, and patients from cohort B (pre-treated) will receive ADT without having been randomized.	Drug: bicalutamide + triptorelin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is a primary outcome for cohort A	37 months after First Patient In
Response rate (RR)	RR is a primary outcome for cohort B	37 months after First Patient In

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (RR)	RR is a secondary outcome for cohort A	37 months after First Patient In
Progression Free Survival (PFS)	PFS is a secondary outcome for cohort B	37 months after First Patient In

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		37 months after First Patient In
Adverse Events according to CTCAE v4.0	adverse events will be recorded using International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, the investigator will assess whether those events are drug related (reasonable possibility, no reasonable possibility) and this assessment will be recorded in the database for all adverse events	37 months after First Patient In

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Principal Investigator: Lisa Licitra, Fondazione IRCCS Istituto Nazionale Tumori; Study Chair: Kevin Harrington, The Royal Marsden

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2015
• Primary Completion (Actual): August 23, 2023
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: October 21, 2013
• First Posted (Estimated): October 25, 2013

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: androgen deprivation; androgen receptor; salivary duct cancer; adenocarcinoma, NOS
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Salivary Gland Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgen Antagonists; Luteolytic Agents; Carboplatin; Paclitaxel; Doxorubicin; Bicalutamide; Triptorelin Pamoate
• Other Study ID Numbers: EORTC-1206; 2013-000314-38 (EudraCT Number)