Back to resultsDarolutamide in Patients With Androgen Receptor-Positive Salivary Gland Carcinoma (DISCOVARY)
Primary Purpose
Salivary Gland Cancer
Status
Active
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Darolutamide
Goserelin
Sponsored by
About this trial
This is an interventional treatment trial for Salivary Gland Cancer focused on measuring Androgen receptor (AR)-positive, Salivary gland carcinoma, Darolutamide, luteinizing hormone-releasing hormone (LH-RH) analogue
Eligibility Criteria
Inclusion Criteria: Darolutamide monotherapy group: Signed, written informed consent. Patients older than 20 years. Histologically confirmed any salivary duct carcinoma (SDC), adenocarcinoma (AC)(NOS), or Carcinoma ex pleomorphic adenoma. Patients with locally recurrent(unresectable) or metastatic salivary gland carcinoma who are not applied for surgery or radiation treatment. Presence of measurable or evaluable disease according to RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Adequate organ or bone marrow function Patients who agree to practice effective barrier contraception and refrain from sperm donation during the entire study treatment period and 3 months after the last dose of the study drug. Darolutamide and Goserelin combination therapy group: Signed, written informed consent. Patients older than 20 years. Histologically confirmed as androgen receptor-positive salivary gland carcinoma at the medical institution. Histologically confirmed as salivary gland carcinoma at the medical institution. Patients with locally recurrent(unresectable) or metastatic salivary gland carcinoma who are not applied for surgery or radiation treatment. Presence of measurable or evaluable disease according to RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Adequate organ or bone marrow function Patients who agree to practice effective barrier contraception refrain from sperm donation and stop breastfeeding during the entire study treatment period and through 3 months after the last dose of the study drug. Exclusion Criteria: Darolutamide monotherapy group: Histologically confirmed as androgen receptor-negative salivary gland carcinoma at a central laboratory. Prior treatment with AR inhibitors, CYP17 enzyme inhibitors, or LH-RH analogue. Metastases in the brain/central nervous system (CNS). Patients who are pregnant or breastfeeding. Synchronous or metachronous malignancies. Participant has a known history of HIV infection. A positive test result for any of the followings: HBsAg positive HBsAb positive and hepatitis B virus (HBV)-DNA positive HBcAb positive and HBV-DNA positive Severe or uncontrolled concurrent heart disease or hypertension. Inability to swallow oral medications. Darolutamide and Goserelin combination therapy group: Prior treatment with AR inhibitors, CYP17 enzyme inhibitors, LH-RH analogue, Sex Hormones, or Gonadotropin Prior treatment with Darolutamide or Goserelin. Metastases in the brain/CNS. Patients who are pregnant or breastfeeding. Synchronous or metachronous malignancies. Participant has a known history of HIV infection. A positive test result for any of the followings: HBsAg positive HBsAb positive and HBV-DNA positive HBcAb positive and HBV-DNA positive Severe or uncontrolled concurrent heart disease or hypertension. Inability to administer Darolutamide or Goserelin.
Sites / Locations
- Nagoya University Hospital
- National Cancer Center Hospital East
- Hokkaido University Hospital
- Kobe University Hospital
- Yokohama City University Hospital
- Tohoku University Hospital
- Chiba University Hospital
- National Hospital Organization Kyushu Medical Center
- Osaka International Cancer Institute
- The Jikei University Hospital
- Tokyo Medical And Dental University Hospital
- Tokyo Medical University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Darolutamide monotherapy
Darolutamide plus Goserelin
Arm Description
Targeted patients: 24
Targeted patients: 32
Outcomes
Primary Outcome Measures
Darolutamide monotherapy group: Objective response rate(ORR) assessed by investigators
The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators
Darolutamide and Goserelin combination therapy group: Objective response rate(ORR) assessed by an Independent Review Committee
The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Secondary Outcome Measures
Duration of Response (DOR)
DOR will be defined 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.
Best Overall Response (BOR)
BOR will be defined as the best response recorded from the start of protocol treatment based on RECIST version 1.1
Disease Control Rate (DCR)
DCR will be defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or SD for at least 6 weeks based on RECIST version 1.1.
Clinical Benefit Rate (CBR)
CBR will be 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.
Clinical Benefit Duration (CBD)
CBD will be defined the period starting from the date of enrollment (start of treatment) and ending on the earlier of the date of determination of progression, the date of death from any cause, or the end of the study period.
Progression-Free Survival (PFS)
PFS will be 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.
Overall Survival (OS)
OS will be defined as the time from the date of the initial dose of study intervention to the date of the participant's death
Adverse events
All adverse events, adverse events with undeniable causal relationship to the investigational drug, severe adverse events (SAEs) and SAEs with undeniable causal relationship to the investigational drug will be evaluated based on CTCAE version 5.0
Quality of Life assessed using the EuroQol-5Dimention-5Level (EQ-5D-5L) questionnaire
Changes from baseline to each time point in health-related quality of life will be measured using the European Quality of Life Five Dimension Five Level Scale Assessment Questionnaire (EQ-5D-5L). The EQ-5D-5L consists of a description and a health assessment. The health description consists of five dimensions (mobility, self-care, normal activities, pain / discomfort, and anxiety / depression), with each dimension identifying five levels of severity [best (1) - worst (5)]. Health assessment is assessed using a visual analogue scale (VAS)([worse (0) - better (100)].
Darolutamide monotherapy group: ORR assessed by an Independent Review Committee
The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Darolutamide and Goserelin combination therapy group: ORR assessed by investigators
The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators
Comparison of androgen receptor (AR) test results in Darolutamide and Goserelin combination therapy group
Comparison of AR test results between each institutional and a central assessment
Positivity of Ki-67 in Darolutamide and Goserelin combination therapy group
The proportion of patients who have high expression of Ki-67 by a central assessment
Full Information
NCT ID
NCT05694819
First Posted
January 12, 2023
Last Updated
September 20, 2023
Sponsor
National Cancer Center Hospital East
Collaborators
Bayer Yakuhin, Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05694819
Brief Title
Darolutamide in Patients With Androgen Receptor-Positive Salivary Gland Carcinoma (DISCOVARY)
Official Title
Phase II Study of Darolutamide (ODM-201) in Patients With Androgen Receptor-positive Salivary Gland Carcinoma (Discovary Study)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 17, 2020 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Center Hospital East
Collaborators
Bayer Yakuhin, Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is an open-label phase 2 study to evaluate the safety and efficacy of Darolutamide monotherapy in patients with androgen receptor-positive salivary gland carcinoma. Moreover, this study will evaluate the safety and efficacy of Darolutamide and Goserelin combination in patients with androgen receptor-positive salivary gland carcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Salivary Gland Cancer
Keywords
Androgen receptor (AR)-positive, Salivary gland carcinoma, Darolutamide, luteinizing hormone-releasing hormone (LH-RH) analogue
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Darolutamide monotherapy
Arm Type
Experimental
Arm Description
Targeted patients: 24
Arm Title
Darolutamide plus Goserelin
Arm Type
Experimental
Arm Description
Targeted patients: 32
Intervention Type
Drug
Intervention Name(s)
Darolutamide
Intervention Description
Darolutamide at a dose of 600 mg (2 tablets of 300 mg) twice daily with food (equivalent to a daily dose of 1200 mg) will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Goserelin
Intervention Description
Goserelin at a dose of 3.6 mg will be administered subcutaneously every 4 weeks.
Primary Outcome Measure Information:
Title
Darolutamide monotherapy group: Objective response rate(ORR) assessed by investigators
Description
The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators
Time Frame
Up to 13 month
Title
Darolutamide and Goserelin combination therapy group: Objective response rate(ORR) assessed by an Independent Review Committee
Description
The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Time Frame
Up to 13 month
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
DOR will be defined 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.
Time Frame
Up to 13 month
Title
Best Overall Response (BOR)
Description
BOR will be defined as the best response recorded from the start of protocol treatment based on RECIST version 1.1
Time Frame
Up to 13 month
Title
Disease Control Rate (DCR)
Description
DCR will be defined as the percentage of participants who achieved a confirmed best overall response of CR, PR, or SD for at least 6 weeks based on RECIST version 1.1.
Time Frame
Up to 13 month
Title
Clinical Benefit Rate (CBR)
Description
CBR will be 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.
Time Frame
Up to 13 month
Title
Clinical Benefit Duration (CBD)
Description
CBD will be defined the period starting from the date of enrollment (start of treatment) and ending on the earlier of the date of determination of progression, the date of death from any cause, or the end of the study period.
Time Frame
Up to 13 month
Title
Progression-Free Survival (PFS)
Description
PFS will be 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.
Time Frame
Up to 13 month
Title
Overall Survival (OS)
Description
OS will be 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 month
Title
Adverse events
Description
All adverse events, adverse events with undeniable causal relationship to the investigational drug, severe adverse events (SAEs) and SAEs with undeniable causal relationship to the investigational drug will be evaluated based on CTCAE version 5.0
Time Frame
Up to 30 days after the last dose
Title
Quality of Life assessed using the EuroQol-5Dimention-5Level (EQ-5D-5L) questionnaire
Description
Changes from baseline to each time point in health-related quality of life will be measured using the European Quality of Life Five Dimension Five Level Scale Assessment Questionnaire (EQ-5D-5L). The EQ-5D-5L consists of a description and a health assessment. The health description consists of five dimensions (mobility, self-care, normal activities, pain / discomfort, and anxiety / depression), with each dimension identifying five levels of severity [best (1) - worst (5)]. Health assessment is assessed using a visual analogue scale (VAS)([worse (0) - better (100)].
Time Frame
Up to 30 days after the last dose
Title
Darolutamide monotherapy group: ORR assessed by an Independent Review Committee
Description
The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Time Frame
Up to 13 month
Title
Darolutamide and Goserelin combination therapy group: ORR assessed by investigators
Description
The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators
Time Frame
Up to 13 month
Title
Comparison of androgen receptor (AR) test results in Darolutamide and Goserelin combination therapy group
Description
Comparison of AR test results between each institutional and a central assessment
Time Frame
Baseline
Title
Positivity of Ki-67 in Darolutamide and Goserelin combination therapy group
Description
The proportion of patients who have high expression of Ki-67 by a central assessment
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Darolutamide monotherapy group:
Signed, written informed consent.
Patients older than 20 years.
Histologically confirmed any salivary duct carcinoma (SDC), adenocarcinoma (AC)(NOS), or Carcinoma ex pleomorphic adenoma.
Patients with locally recurrent(unresectable) or metastatic salivary gland carcinoma who are not applied for surgery or radiation treatment.
Presence of measurable or evaluable disease according to RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Adequate organ or bone marrow function
Patients who agree to practice effective barrier contraception and refrain from sperm donation during the entire study treatment period and 3 months after the last dose of the study drug.
Darolutamide and Goserelin combination therapy group:
Signed, written informed consent.
Patients older than 20 years.
Histologically confirmed as androgen receptor-positive salivary gland carcinoma at the medical institution.
Histologically confirmed as salivary gland carcinoma at the medical institution.
Patients with locally recurrent(unresectable) or metastatic salivary gland carcinoma who are not applied for surgery or radiation treatment.
Presence of measurable or evaluable disease according to RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Adequate organ or bone marrow function
Patients who agree to practice effective barrier contraception refrain from sperm donation and stop breastfeeding during the entire study treatment period and through 3 months after the last dose of the study drug.
Exclusion Criteria:
Darolutamide monotherapy group:
Histologically confirmed as androgen receptor-negative salivary gland carcinoma at a central laboratory.
Prior treatment with AR inhibitors, CYP17 enzyme inhibitors, or LH-RH analogue.
Metastases in the brain/central nervous system (CNS).
Patients who are pregnant or breastfeeding.
Synchronous or metachronous malignancies.
Participant has a known history of HIV infection.
A positive test result for any of the followings:
HBsAg positive
HBsAb positive and hepatitis B virus (HBV)-DNA positive
HBcAb positive and HBV-DNA positive
Severe or uncontrolled concurrent heart disease or hypertension.
Inability to swallow oral medications.
Darolutamide and Goserelin combination therapy group:
Prior treatment with AR inhibitors, CYP17 enzyme inhibitors, LH-RH analogue, Sex Hormones, or Gonadotropin
Prior treatment with Darolutamide or Goserelin.
Metastases in the brain/CNS.
Patients who are pregnant or breastfeeding.
Synchronous or metachronous malignancies.
Participant has a known history of HIV infection.
A positive test result for any of the followings:
HBsAg positive
HBsAb positive and HBV-DNA positive
HBcAb positive and HBV-DNA positive
Severe or uncontrolled concurrent heart disease or hypertension.
Inability to administer Darolutamide or Goserelin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Makoto Tahara, MD, PhD
Organizational Affiliation
National Cancer Center Hospital East
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Naomi Kiyota, MD, PhD
Organizational Affiliation
Kobe University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Susumu Okano, MD, PhD
Organizational Affiliation
National Cancer Center Hospital East
Official's Role
Study Chair
Facility Information:
Facility Name
Nagoya University Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Yokohama City University Hospital
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
236-0004
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Chiba University Hospital
City
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
National Hospital Organization Kyushu Medical Center
City
Fukuoka
ZIP/Postal Code
810-8563
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
The Jikei University Hospital
City
Tokyo
ZIP/Postal Code
105-0003
Country
Japan
Facility Name
Tokyo Medical And Dental University Hospital
City
Tokyo
ZIP/Postal Code
113-8519
Country
Japan
Facility Name
Tokyo Medical University Hospital
City
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
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Darolutamide in Patients With Androgen Receptor-Positive Salivary Gland Carcinoma (DISCOVARY)
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