A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma

Salivary Gland Neoplasms Clinical Trial

— YATAGARASU  

Official title:

An Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Apalutamide in Combination With Gonadotropin-releasing Hormone (GnRH) Agonist in Subjects With Locally Advanced or Recurrent/Metastatic and Androgen Receptor (AR) Expressing Salivary Gland Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04325828
• Other study ID #: CR108758
• Secondary ID: 56021927SGT2001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 7, 2020
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the overall response rate (ORR) of apalutamide in combination with a gonadotropin-releasing hormone (GnRH) agonist in participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: September 30, 2025
• Est. primary completion date: June 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed salivary gland carcinoma (SGC) by local pathology

• Androgen receptor (AR) expressing SGC: Local testing of AR-positivity will be performed as standard of care for the eligibility confirmation. AR-positivity will be defined according to immunohistochemistry (IHC) staining of tumor tissue with at least 1 percent (%) of cell nuclei staining positive. Tissue should be available for the central confirmation of AR-positivity, but the central result of AR positivity will not be required for initiating the study intervention

• Locally advanced or recurrent/metastatic SGC

• Measurable lesion(s) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to first dose. Treatment with a drug that has a short half life (t1/2) (for example, less than [<] 1 day) may be eligible in accordance with the discussion with the sponsor's medical monitor

• Radiographically confirmed brain metastases. In case of history of brain metastases that were previously treated and not recurred for at least 6 months, they are considered eligible

• Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less (except for all grade alopecia, and for peripheral neuropathy, and hypothyroidism stable on hormone replacement therapy to be Grade 2 or less). If corticosteroids are administered for any reasons such as the management of toxicities due to prior therapies, the dose must be tapered until 10 milligram (mg)/day or less of prednisolone and contact the sponsor's medical monitor on an individual basis prior to the first dose

• Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction

• History of seizure or any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness less than or equal to [<=] 1 year prior to first dose; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)

• Treatment with drugs known to lower the seizure threshold within 4 weeks prior to first dose

• Known or suspected contraindications or hypersensitivity to apalutamide, gonadotropin-releasing hormone agonist (GnRHa) analogues or any of the components of the formulations

• Received prior ADT including a GnRH analogue, AR blocker such as bicalutamide, enzalutamide or 17alpha-hydroxylase-17,20-lyase (CYP17) inhibitor such as abiraterone acetate etc. Chemotherapy, radiation, or surgery as part of curative intent therapy are allowed so long as prior therapy did not include ADT. Prior chemotherapy, targeted cancer therapy or immunotherapy within 1 week or 4 half-lives whichever is longer, before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 2 weeks

Related Conditions & MeSH terms

• Salivary Gland Neoplasms

Intervention

Drug:
• Apalutamide
Apalutamide 240 mg (4*60-mg tablets) will be administered orally once daily with or without food.
• GnRH Agonist
A stable regimen of goserelin 3.6 mg will be administered as a GnRH agonist.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	Kansai Medical University Hospital	Hirakata
Japan	National Hospital Organizaiton Shikoku Cancer Center	Matsuyama
Japan	Aichi Cancer Center Hospital	Nagoya Shi
Japan	Niigata University Medical And Dental Hospital	Niigata
Japan	Hokkaido University Hospital	Sapporo-shi

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Overall response rate (ORR) was defined as the percentage of participants who achieve partial response (PR) or better according to the response evaluation criteria in solid tumors (RECIST) version1.1, including with either confirmed best overall response of complete response (CR) or PR during the study. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR is defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.	Up to 13 months
Secondary	Clinical Benefit Rate (CBR)	Clinical benefit rate (CBR) was defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or stable disease (SD) for at least 24 weeks based on RECIST version 1.1 during the study (and prior to subsequent therapy if any). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.	Up to 13 months
Secondary	Disease Control Rate (DCR)	DCR was defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or SD based on RECIST version 1.1 during the study (and prior to subsequent therapy if any). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.	Up to 13 months
Secondary	Progression-free Survival (PFS) as Assessed by ICRR	PFS was defined as the time from the date of the initial dose of study intervention to the date of first documented disease progression as defined in the RECIST version 1.1, or death due to any cause, whichever occurred first. Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.	Up to 13 months
Secondary	Overall Survival (OS)	Overall survival (OS) was defined as the time from the date of the initial dose of study intervention to the date of the participant's death.	Up to 13 months
Secondary	Time to Response (TTR)	TTR was defined among responders (with a CR or PR) as the time between date of the initial dose of study intervention and the first efficacy evaluation that the participant had met all criteria for CR or PR. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.	Up to 13 months
Secondary	Duration of Response (DoR)	DoR calculated among responders from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease as defined in RECIST version 1.1 or death, whichever occurred first. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, in absence of new lesions or unequivocal progression of non-target lesions.	Up to 13 months
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Number of participants with TEAEs were reported. Treatment-emergent adverse events (TEAEs) for the treatment phase included events with an onset date/time on or after the start of study intervention through the day of last dose plus 30 days were considered as treatment-emergent.	Up to 13 months
Secondary	Plasma Concentration of Apalutamide	Plasma concentration of apalutamide was reported.	Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)
Secondary	Plasma Concentration of N-desmethyl Apalutamide	Plasma concentration of N-desmethyl Apalutamide was reported.	Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)