Abiraterone Acetate in Patients With Relapsed and/or Metastatic Salivary Gland Cancers (SG-ABI14)

Phase II Trial of Abiraterone Acetate in Patients With Relapsed and/or Metastatic, Castration Resistant Salivary Gland Cancers

Carcinomas of the salivary glands (SGCs) are rare tumors. Some selected salivary gland histotypes such as salivary duct carcinomas (SDC) and adenocarcinomas, NOS (not otherwise specified) distinguish themselves for the expression of androgen receptors (AR), which is reported in 21% to 43% of the cases. Thus, similarly to prostate cancer (Pca), androgen deprivation therapy (ADT) has been suggested to be beneficial in patients with recurrent or disseminated AR-expressing disease. No other therapy except palliative chemotherapy is available after progression on ADT, thus underling the necessity of alternative therapeutic approaches.

Study Overview

• Status: Completed
• Conditions: Salivary Glands Tumors
• Intervention / Treatment: Drug: Abiraterone acetate

Detailed Description

Carcinomas of the salivary glands (SGC) are rare tumors. They comprise less than 1% of all cancers of the head and neck. The standard treatment is surgical excision, followed by radiotherapy in selected cases, such as high-grade tumors, and/or in the presence of perineural invasion, and/or in the presence of advanced disease. Some selected salivary gland histotypes such as salivary duct carcinomas (SDC) and adenocarcinomas, NOS (not otherwise specified) distinguish themselves for the expression of androgen receptors (AR), which is reported in 21% to 43% of the cases. Thus, similarly to prostate cancer (Pca), androgen deprivation therapy (ADT) has been suggested to be beneficial in patients with recurrent or disseminated AR-expressing disease.

The proven activity of ADT in AR expressing SGC as well as in Pca, suggests a common clinical behaviour by apparently sharing the same biological background. Once Pca becomes resistant to castration it still remains driven by ligand-dependent AR signaling and further hormonal manipulations are active and efficacious. Abiraterone acetate is currently approved by FDA for castration-resistant prostate cancer (CRPC). We treated with abiraterone two patients with AR-positive adenocarcinoma who had progressed on ADT, both patients showed a partial response suggesting the activity of a second line hormonal therapy in SGCs.

Based on the above biological and clinical evidences, the aim of the trial is to assess the activity of abiraterone in AR-expressing castration resistant SGCs.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione Irccs Istituto Nazionale Dei Tumori

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent
• Age ≥18 years
• Histologically or cytologically confirmed salivary glands cancer
• At least, one target lesion defined as RECIST 1.1 (clear progression of disease is required in the presence of one target lesion previously treated with radiotherapy
• Clinical and/or radiological progression of disease on ADT
• Ongoing androgen deprivation with a serum testosterone level of less than 50 ng per deciliter (1.7 nmol per liter)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
• Adequate bone marrow function: Neutrophils > 1.5 x 109/L; Hemoglobin ≥ 9.0 g/dL independent of transfusion and platelet count ≥ 100,000/μL
• No limits are required for the number of previous chemotherapy lines
• Serum albumin ≥ 3.0 g/dL
• Serum creatinine <1.5 x upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 mL/min
• Serum potassium ≥3.5 mmol/L
• Able to swallow the study drug whole as a tablet
• Patients with treated brain metastases, stable within the last three months, are allowed
• Subjects who have partners of childbearing potential must use a method of birth control with adequate barrier protection as determined to be acceptable by the investigator and for 13 weeks after last study drug administration

Exclusion Criteria:

• Received abiraterone acetate within the last 5 years
• Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
• Abnormal liver functions consisting of any of the following:
• Serum bilirubin ≥ 1.5 x ULN (except for subjects with documented Gilbert's disease, for whom the upper limit of serum bilirubin is 3 mg/dL)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5 x ULN
• Patients with ALT and/or AST not exceeding 5 x ULN due to liver mets can be enrolled
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg); subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or left ventricular ejection fraction (LVEF) of <50% at baseline
• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study drug
• Any acute toxicities due to prior chemotherapy or radiotherapy that have not resolved to a NCI-CTCAE (Version 4.0) Grade of ≤1
• Participation in clinical trials with other experimental agents within 30 days of study entry or concomitant treatment with other experimental drug
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1) or any cancer curatively treated > 3 years prior to study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abiraterone acetate; Abiraterone acetate 1 g/day must be taken as four 250-mg tablets daily on an empty stomach. No food should be consumed for at least 2 hours before the dose of abiraterone acetate is taken and for at least 1 hour after the dose of abiraterone acetate is taken. Prednisone (prednisolone when prednisone is not available) 5 mg will be given orally twice a day.	Drug: Abiraterone acetate; Abiraterone acetate is a prodrug of abiraterone, an irreversible inhibitor of 17α hydroxylase/C17, 20-lyase (cytochrome P450c17 [CYP17]), a key enzyme required for testosterone synthesis. This enzyme is found in the testes, adrenals, prostate tumors; Other Names: Zytiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	The assessment of the activity considered as the response rate of abiraterone acetate in castration resistant salivary glands cancer	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	The assessment of disease control rate of abiraterone acetate in castration resistant salivary glands cancer	4 years
Adverse Events incidence	Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0	4 years
Progression free survival	The assessment of progression free survival of patients suffering from castration resistant salivary glands cancer enrolled and treated wuth abiraterone acetate	4 years
Overall survival	The assessment of overall survival of patients suffering from castration resistant salivary glands cancer enrolled and treated wuth abiraterone acetate	4 years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Lisa Licitra, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

General Publications

• Locati LD, Cavalieri S, Bergamini C, Resteghini C, Colombo E, Calareso G, Mariani L, Quattrone P, Alfieri S, Bossi P, Platini F, Capone I, Licitra L. Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial. J Clin Oncol. 2021 Dec 20;39(36):4061-4068. doi: 10.1200/JCO.21.00468. Epub 2021 Oct 1.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): November 1, 2019
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: August 11, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (Estimate): August 16, 2016

Study Record Updates

• Last Update Posted (Actual): March 3, 2021
• Last Update Submitted That Met QC Criteria: March 1, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Abiraterone Acetate
• Other Study ID Numbers: INT 71/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Abstract presentation to National and International congresses and final data publication on indexed papers