Androgen Deprivation Therapy in Advanced Salivary Gland Cancer

Salivary Gland Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01969578
• Other study ID #: EORTC-1206
• Secondary ID: 2013-000314-38
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 24, 2015
• Est. completion date: July 31, 2024

Study information

• Verified date: September 2023
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 149
• Est. completion date: July 31, 2024
• Est. primary completion date: August 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Salivary Gland Cancer
• Salivary Gland Neoplasms

Intervention

Drug:
• bicalutamide + triptorelin

• Cisplatin + Doxorubicin

• Carboplatin + Paclitaxel

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival (OS)		37 months after First Patient In
Other	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
Primary	Progression Free Survival (PFS)	PFS is a primary outcome for cohort A	37 months after First Patient In
Primary	Response rate (RR)	RR is a primary outcome for cohort B	37 months after First Patient In
Secondary	Response Rate (RR)	RR is a secondary outcome for cohort A	37 months after First Patient In
Secondary	Progression Free Survival (PFS)	PFS is a secondary outcome for cohort B	37 months after First Patient In