Darolutamide in Patients With Androgen Receptor-Positive Salivary Gland Carcinoma (DISCOVARY)

Salivary Gland Cancer Clinical Trial

Official title:

Phase II Study of Darolutamide (ODM-201) in Patients With Androgen Receptor-positive Salivary Gland Carcinoma (Discovary Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05694819
• Other study ID #: YCU19003
• Secondary ID: jRCT2031190241
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 17, 2020
• Est. completion date: February 2026

Study information

• Verified date: June 2024
• Source: National Cancer Center Hospital East
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 56
• Est. completion date: February 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

Darolutamide monotherapy group:

1. Signed, written informed consent.

2. Patients older than 20 years.

3. Histologically confirmed any salivary duct carcinoma (SDC), adenocarcinoma (AC)(NOS), or Carcinoma ex pleomorphic adenoma.

4. Patients with locally recurrent(unresectable) or metastatic salivary gland carcinoma who are not applied for surgery or radiation treatment.

5. Presence of measurable or evaluable disease according to RECIST v1.1

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

7. Adequate organ or bone marrow function

8. 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:

1. Signed, written informed consent.

2. Patients older than 20 years.

3. Histologically confirmed as androgen receptor-positive salivary gland carcinoma at the medical institution.

4. Histologically confirmed as salivary gland carcinoma at the medical institution.

5. Patients with locally recurrent(unresectable) or metastatic salivary gland carcinoma who are not applied for surgery or radiation treatment.

6. Presence of measurable or evaluable disease according to RECIST v1.1

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

8. Adequate organ or bone marrow function

9. 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:

1. Histologically confirmed as androgen receptor-negative salivary gland carcinoma at a central laboratory.

2. Prior treatment with AR inhibitors, CYP17 enzyme inhibitors, or LH-RH analogue.

3. Metastases in the brain/central nervous system (CNS).

4. Patients who are pregnant or breastfeeding.

5. Synchronous or metachronous malignancies.

6. Participant has a known history of HIV infection.

7. 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

8. Severe or uncontrolled concurrent heart disease or hypertension.

9. Inability to swallow oral medications.

Darolutamide and Goserelin combination therapy group:

1. Prior treatment with AR inhibitors, CYP17 enzyme inhibitors, LH-RH analogue, Sex Hormones, or Gonadotropin

2. Prior treatment with Darolutamide or Goserelin.

3. Metastases in the brain/CNS.

4. Patients who are pregnant or breastfeeding.

5. Synchronous or metachronous malignancies.

6. Participant has a known history of HIV infection.

7. A positive test result for any of the followings:

• HBsAg positive

• HBsAb positive and HBV-DNA positive

• HBcAb positive and HBV-DNA positive

8. Severe or uncontrolled concurrent heart disease or hypertension.

9. Inability to administer Darolutamide or Goserelin.

Related Conditions & MeSH terms

• Carcinoma
• Salivary Gland Cancer
• Salivary Gland Neoplasms

Intervention

Drug:
• Darolutamide
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.
• Goserelin
Goserelin at a dose of 3.6 mg will be administered subcutaneously every 4 weeks.

Locations

Country	Name	City	State
Japan	Chiba University Hospital	Chiba
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Osaka International Cancer Institute	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	The Jikei University Hospital	Tokyo
Japan	Tokyo Medical And Dental University Hospital	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Yokohama City University Hospital	Yokohama	Kanagawa

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Center Hospital East	Bayer Yakuhin, Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 13 month
Primary	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	Up to 13 month
Secondary	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.	Up to 13 month
Secondary	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	Up to 13 month
Secondary	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.	Up to 13 month
Secondary	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.	Up to 13 month
Secondary	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.	Up to 13 month
Secondary	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.	Up to 13 month
Secondary	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	Up to 13 month
Secondary	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	Up to 30 days after the last dose
Secondary	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)].	Up to 30 days after the last dose
Secondary	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	Up to 13 month
Secondary	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	Up to 13 month
Secondary	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	Baseline
Secondary	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	Baseline