Clinical Trials /

Androgen Deprivation Therapy in Advanced Salivary Gland Cancer

NCT01969578

Description:

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.

Related Conditions:
  • Salivary Duct Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: EORTC-1206
  • SECONDARY ID: 2013-000314-38
  • NCT ID: NCT01969578

Conditions

  • Salivary Gland Cancer

Interventions

DrugSynonymsArms
bicalutamide + triptorelinAndrogen Deprivation Therapy (ADT)
Cisplatin + DoxorubicinChemotherapy
Carboplatin + PaclitaxelChemotherapy

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ChemotherapyActive ComparatorChemotherapy = either Cisplatin + Doxorubicin or Carboplatin + Paclitaxel Patients from cohort A (chemonaïve) may be randomized in this arm to receive chemotherapy
  • Cisplatin + Doxorubicin
  • Carboplatin + Paclitaxel
Androgen Deprivation Therapy (ADT)ExperimentalADT = 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.
  • bicalutamide + triptorelin

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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:37 months after First Patient In
Safety Issue:
Description:PFS is a primary outcome for cohort A

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

Trial Keywords

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

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