Androgen Deprivation Therapy in Advanced Salivary Gland Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01969578
First received: September 24, 2013
Last updated: February 28, 2014
Last verified: February 2014
  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.


Condition Intervention Phase
Salivary Gland Cancer
Drug: bicalutamide + triptorelin
Drug: Cisplatin + Doxorubicin
Drug: Carboplatin + Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 37 months after First Patient In ] [ Designated as safety issue: No ]
    PFS is a primary outcome for cohort A

  • Response rate (RR) [ Time Frame: 37 months after First Patient In ] [ Designated as safety issue: No ]
    RR is a primary outcome for cohort B


Secondary Outcome Measures:
  • Response Rate (RR) [ Time Frame: 37 months after First Patient In ] [ Designated as safety issue: No ]
    RR is a secondary outcome for cohort A

  • Progression Free Survival (PFS) [ Time Frame: 37 months after First Patient In ] [ Designated as safety issue: No ]
    PFS is a secondary outcome for cohort B


Other Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 37 months after First Patient In ] [ Designated as safety issue: No ]
  • Adverse Events according to CTCAE v4.0 [ Time Frame: 37 months after First Patient In ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 152
Study Start Date: June 2014
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 left ventricular ejection fraction (LVEF) ≥ 50% and a clinically normal 12 lead ECG

Exclusion Criteria:

  • 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;
  • history of allergic reactions attributed to compounds of similar chemical or biological composition to cis/carboplatin, paclitaxel, doxorubicin, bicalutamide or triptorelin;
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01969578

Contacts
Contact: Leslie Herman +32 2 774 15 11 leslie.herman@eortc.be

Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Principal Investigator: Lisa Licitra Fondazione IRCCS Istituto Nazionale Tumori
Study Chair: Alan Ho Memorial Sloan-Kettering Cancer Center
Study Chair: Kevin Harrington The Royal Marsden
  More Information

No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01969578     History of Changes
Other Study ID Numbers: EORTC-1206-HNCG, 2013-000314-38
Study First Received: September 24, 2013
Last Updated: February 28, 2014
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
salivary duct cancer
adenocarcinoma, NOS
androgen deprivation
androgen receptor

Additional relevant MeSH terms:
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Salivary Gland Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Paclitaxel
Liposomal doxorubicin
Bicalutamide
Cisplatin
Carboplatin
Doxorubicin
Triptorelin Pamoate
Androgens
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Hormones

ClinicalTrials.gov processed this record on September 22, 2014