Back to resultsA Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma (YATAGARASU)
Primary Purpose
Salivary Gland Neoplasms
Status
Active
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Apalutamide
GnRH Agonist
Sponsored by
About this trial
This is an interventional treatment trial for Salivary Gland Neoplasms
Eligibility Criteria
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
Sites / Locations
- National Cancer Center Hospital
- National Hospital Organization Kyushu Medical Center
- Kansai Medical University Hospital
- National Hospital Organizaiton Shikoku Cancer Center
- Aichi Cancer Center Hospital
- Niigata University Medical & Dental Hospital
- Hokkaido University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Apalutamide plus GnRH Agonist
Arm Description
Participants will receive apalutamide 240 milligram (mg) in combination with a gonadotropin-releasing hormone (GnRH) agonist until disease progression, unacceptable toxicity, death, or the end of the study and each treatment cycle will be of 28 days. Participants who are benefitting from this study will enter long term extension phase.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Plasma Concentration of Apalutamide
Plasma concentration of apalutamide was reported.
Plasma Concentration of N-desmethyl Apalutamide
Plasma concentration of N-desmethyl Apalutamide was reported.
Full Information
NCT ID
NCT04325828
First Posted
March 26, 2020
Last Updated
October 11, 2023
Sponsor
Janssen Pharmaceutical K.K.
1. Study Identification
Unique Protocol Identification Number
NCT04325828
Brief Title
A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 7, 2020 (Actual)
Primary Completion Date
June 9, 2021 (Actual)
Study Completion Date
May 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Pharmaceutical K.K.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Salivary Gland Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Apalutamide plus GnRH Agonist
Arm Type
Experimental
Arm Description
Participants will receive apalutamide 240 milligram (mg) in combination with a gonadotropin-releasing hormone (GnRH) agonist until disease progression, unacceptable toxicity, death, or the end of the study and each treatment cycle will be of 28 days. Participants who are benefitting from this study will enter long term extension phase.
Intervention Type
Drug
Intervention Name(s)
Apalutamide
Other Intervention Name(s)
JNJ-56021927
Intervention Description
Apalutamide 240 mg (4*60-mg tablets) will be administered orally once daily with or without food.
Intervention Type
Drug
Intervention Name(s)
GnRH Agonist
Intervention Description
A stable regimen of goserelin 3.6 mg will be administered as a GnRH agonist.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 13 months
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate (CBR)
Description
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.
Time Frame
Up to 13 months
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
Up to 13 months
Title
Progression-free Survival (PFS) as Assessed by ICRR
Description
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.
Time Frame
Up to 13 months
Title
Overall Survival (OS)
Description
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.
Time Frame
Up to 13 months
Title
Time to Response (TTR)
Description
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.
Time Frame
Up to 13 months
Title
Duration of Response (DoR)
Description
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.
Time Frame
Up to 13 months
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Up to 13 months
Title
Plasma Concentration of Apalutamide
Description
Plasma concentration of apalutamide was reported.
Time Frame
Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)
Title
Plasma Concentration of N-desmethyl Apalutamide
Description
Plasma concentration of N-desmethyl Apalutamide was reported.
Time Frame
Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Pharmaceutical K.K., Japan Clinical Trial
Organizational Affiliation
Janssen Pharmaceutical K.K.
Official's Role
Study Director
Facility Information:
Facility Name
National Cancer Center Hospital
City
Chuo-Ku
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
National Hospital Organization Kyushu Medical Center
City
Fukuoka
ZIP/Postal Code
810-8563
Country
Japan
Facility Name
Kansai Medical University Hospital
City
Hirakata
ZIP/Postal Code
573-1191
Country
Japan
Facility Name
National Hospital Organizaiton Shikoku Cancer Center
City
Matsuyama
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Aichi Cancer Center Hospital
City
Nagoya-Shi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Niigata University Medical & Dental Hospital
City
Niigata
ZIP/Postal Code
951-8520
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo-shi
ZIP/Postal Code
060-8648
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma
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