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

Phase 2

Active, not recruiting

• Conditions: Salivary Gland Cancer
• Interventions: Drug: Darolutamide; Drug: Goserelin

• Registration Number: NCT05694819
• Lead Sponsor: National Cancer Center Hospital East

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-17
• Study First Submitted: 2023-01-12
• Study First Submitted QC: 2023-01-12
• Study First Posted: 2023-01-23
• Primary Completion: 2024-08-09
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-22
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 56

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Darolutamide plus Goserelin	Goserelin	Targeted patients: 32
Darolutamide monotherapy	Darolutamide	Targeted patients: 24
Darolutamide plus Goserelin	Darolutamide	Targeted patients: 32

Primary Outcome Measures

Name	Time	Method
Darolutamide and Goserelin combination therapy group: Objective response rate(ORR) assessed by an Independent Review Committee	Up to 13 month	The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Darolutamide monotherapy group: Objective response rate(ORR) assessed by investigators	Up to 13 month	The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators

Secondary Outcome Measures

Name	Time	Method
Best Overall Response (BOR)	Up to 13 month	BOR will be defined as the best response recorded from the start of protocol treatment based on RECIST version 1.1
Quality of Life assessed using the EuroQol-5Dimention-5Level (EQ-5D-5L) questionnaire	Up to 30 days after the last dose	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)(\[worse (0) - better (100)\].
Clinical Benefit Duration (CBD)	Up to 13 month	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.
Overall Survival (OS)	Up to 13 month	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	Up to 30 days after the last dose	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
Darolutamide monotherapy group: ORR assessed by an Independent Review Committee	Up to 13 month	The proportion of patients with confirmed tumor response of CR or PR per RECIST 1.1, as assessed by an independent review committee
Comparison of androgen receptor (AR) test results in Darolutamide and Goserelin combination therapy group	Baseline	Comparison of AR test results between each institutional and a central assessment
Disease Control Rate (DCR)	Up to 13 month	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.
Progression-Free Survival (PFS)	Up to 13 month	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.
Duration of Response (DOR)	Up to 13 month	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.
Clinical Benefit Rate (CBR)	Up to 13 month	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.
Darolutamide and Goserelin combination therapy group: ORR assessed by investigators	Up to 13 month	The proportion of patients with confirmed tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by investigators
Positivity of Ki-67 in Darolutamide and Goserelin combination therapy group	Baseline	The proportion of patients who have high expression of Ki-67 by a central assessment

Trial Locations

Locations (12)

Hokkaido University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

National Hospital Organization Kyushu Medical Center; 🇯🇵 Fukuoka, Japan

Tohoku University Hospital; 🇯🇵 Sendai, Miyagi, Japan

Kobe University Hospital; 🇯🇵 Kobe, Hyogo, Japan

Chiba University Hospital; 🇯🇵 Chiba, Japan

Tokyo Medical University Hospital; 🇯🇵 Tokyo, Japan

Nagoya University Hospital; 🇯🇵 Nagoya, Aichi, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan

Yokohama City University Hospital; 🇯🇵 Yokohama, Kanagawa, Japan

The Jikei University Hospital; 🇯🇵 Tokyo, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka, Japan

Tokyo Medical And Dental University Hospital; 🇯🇵 Tokyo, Japan