Clinical trial NCT05694819: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Salivary Gland Cancer
Keywords: Androgen receptor (AR)-positive
Salivary gland carcinoma
Darolutamide
luteinizing hormone-releasing hormone (LH-RH) analogue
Lead sponsor: National Cancer Center Hospital East
Sponsor class: OTHER
Collaborators: name: Bayer Yakuhin, Ltd.
First posted: 2023-01-23
Enrollment: 56
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Darolutamide monotherapy group: Objective response rate(ORR) assessed by investigators
timeFrame: Up to 13 month
measure: Darolutamide and Goserelin combination therapy group: Objective response rate(ORR) assessed by an Independent Review Committee
timeFrame: Up to 13 month
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to 13 month
measure: Best Overall Response (BOR)
timeFrame: Up to 13 month
measure: Disease Control Rate (DCR)
timeFrame: Up to 13 month
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 13 month
measure: Clinical Benefit Duration (CBD)
timeFrame: Up to 13 month
measure: Progression-Free Survival (PFS)
timeFrame: Up to 13 month
measure: Overall Survival (OS)
timeFrame: Up to 13 month
measure: Adverse events
timeFrame: Up to 30 days after the last dose
measure: Quality of Life assessed using the EuroQol-5Dimention-5Level (EQ-5D-5L) questionnaire
timeFrame: Up to 30 days after the last dose
measure: Darolutamide monotherapy group: ORR assessed by an Independent Review Committee
timeFrame: Up to 13 month
measure: Darolutamide and Goserelin combination therapy group: ORR assessed by investigators
timeFrame: Up to 13 month
measure: Comparison of androgen receptor (AR) test results in Darolutamide and Goserelin combination therapy group
timeFrame: Baseline
measure: Positivity of Ki-67 in Darolutamide and Goserelin combination therapy group
timeFrame: Baseline
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: The Jikei University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical And Dental University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
Study officials:
affiliation: National Cancer Center Hospital East
name: Makoto Tahara, MD, PhD
role: STUDY_DIRECTOR
affiliation: Kobe University Hospital
name: Naomi Kiyota, MD, PhD
role: STUDY_CHAIR
affiliation: National Cancer Center Hospital East
name: Susumu Okano, MD, PhD
role: STUDY_CHAIR
References: