Androgen Deprivation Therapy in Advanced Salivary Gland Cancer

NCT01969578 | Completed Phase 2 DMC

• 2 other identifiers: EORTC-12062013-000314-38
• Study Type: interventional
• Target: 149
• Locations: 8 countries
• Sites: 26

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.

Conditions

Salivary Gland Cancer

Keywords

salivary duct cancer; adenocarcinoma, NOS; androgen deprivation; androgen receptor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Response Rate (RR)

  37 months after First Patient In

• Progression Free Survival (PFS)

  37 months after First Patient In

Other Outcomes (2)

• Overall Survival (OS)

  37 months after First Patient In

• Adverse Events according to CTCAE v4.0

  37 months after First Patient In

Study Arms (2)

Chemotherapy

ACTIVE COMPARATOR

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

Androgen Deprivation Therapy (ADT)

EXPERIMENTAL

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

Interventions

bicalutamide + triptorelin DRUG

Androgen Deprivation Therapy (ADT)

Cisplatin + Doxorubicin DRUG

Chemotherapy

Carboplatin + Paclitaxel DRUG

Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (26)

Medical University Vienna - General Hospital AKH

Vienna, 1090, Austria

Location

ZNA Middelheim

Antwerp, 2020, Belgium

Location

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, 33075, France

Location

Institut régional du Cancer Montpellier

Montpellier, France

Location

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau

Nantes, 44805, France

Location

CHU de Nantes - Hotel Dieu

Nantes, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Assistance Publique - Hopitaux de Paris - Hopital Tenon

Paris, 75020, France

Location

Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole - Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

Gustave Roussy

Villejuif, France

Location

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

Universitaetsklinikum Jena-Radiation Therapy and Radiooncology Clinic

Jena, 07747, Germany

Location

Universitaetsklinikum Leipzig-Ambulanzen/Sprechstunden

Leipzig, Germany

Location

Athens University - Attikon University General Hospital

Athens, 12462, Greece

Location

National Institute Of Oncology

Budapest, 1122, Hungary

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Azienda Provinciale per i Servizi Sanitari - Ospedale Santa Chiara

Trento, 38100, Italy

Location

Spaarne Gasthuis - Vrije Universiteit Medisch Centrum

Amsterdam, 1007MB, Netherlands

Location

University Medical Center Groningen (UMCG)

Groningen, 9713 GZ, Netherlands

Location

Radboud University Medical Center Nijmegen

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Salivary Gland Neoplasms; Adenocarcinoma; Bulbo-Spinal Atrophy, X-Linked

Interventions

bicalutamide; Triptorelin Pamoate; Cisplatin; Doxorubicin; CP protocol

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Lisa Licitra

  Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

  PRINCIPAL INVESTIGATOR

• Kevin Harrington

  The Royal Marsden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: October 25, 2013
• Study Start: September 24, 2015
• Primary Completion: August 23, 2023
• Study Completion: February 16, 2024
• Last Updated: November 5, 2024

Record last verified: 2024-11

Locations

IT (3); BE (5); NL (3); AU (1); HU (1); DE (3); FR (9); GR (1)