A randomized phase II trial on the addition of dutasteride to combined androgen blockade therapy versus combined androgen blockade therapy alone in patients with recurrent and/or metastatic salivary duct carcinoma – DUCT study

The primary objective of this study is to determine the **efficacy** of dutasteride in combination with combined androgen blockade therapy in patients with recurrent and/or metastatic **salivary duct carcinoma**. This is clinically relevant as it aims to evaluate the potential benefits of adding dutasteride to the existing treatment regimen, which could lead to improved therapeutic outcomes for patients with this aggressive form of cancer.

Secondary objectives include:

• Assessing other indicators of therapy efficacy.
• Evaluating the safety profile of dutasteride when combined with combined androgen blockade therapy.
• Assessing the quality of life of patients treated with this combination therapy.
• Exploring predictive markers of response.
• Assessing the expression of molecular targets and documenting the modulation of response in the tumor microenvironment.

The clinical trial focuses on evaluating the efficacy of dutasteride in combination with combined androgen blockade therapy for patients with **salivary duct carcinoma**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a pathologically or histologically confirmed diagnosis of androgen receptor-positive recurrent and/or metastatic salivary duct carcinoma. The trial does not involve a vulnerable population. Participants must have adequate cardiac, bone marrow, liver, and renal function, as well as a measurable disease per RECIST version 1.1 at baseline. The Eastern Cooperative Oncology Group (ECOG) performance status of participants should be 0 or 1. The sponsor has not provided information regarding the total number of participants in the trial. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **controlled**, and **double-blind** study to evaluate the efficacy of **dutasteride** in combination with combined androgen blockade therapy in patients with recurrent and/or metastatic **salivary duct carcinoma**. The trial is categorized as a Phase II study, focusing on the safety and efficacy of the potential therapy. The trial is expected to run from September 2022 to September 2027, with recruitment having commenced in September 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a pathologically confirmed diagnosis of AR+ recurrent/metastatic salivary duct carcinoma, adequate organ function, and an ECOG performance status of 0 or 1. Following the screening, participants will be randomized to receive either the investigational combination therapy or the control therapy. The trial includes regular follow-up visits to monitor treatment response and safety, with assessments conducted according to RECIST version 1.1 criteria. The primary endpoints include overall response rate and duration of response, while secondary endpoints encompass progression-free survival, overall survival, and quality of life assessments.

The expected duration of participant involvement is up to 20 months, depending on the treatment arm and individual response. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. The end-of-study visit will occur after the completion of the treatment period or upon early termination, during which final assessments will be conducted to evaluate the overall outcomes of the trial.

The clinical trial involves the administration of **Zoladex-10,8**, an implant containing **goserelin acetate** as the active substance. This pharmaceutical form is an implant, specifically an implantatiestaafje, with a dosage of 10.8 mg. The route of administration is via **subcutaneous injection**. The maximum daily dose is 0.12 mg, with a total maximum dose of 43.2 mg over a treatment period of 12 months. The product is manufactured by AstraZeneca BV and is classified under the ATC code L02AE03, indicating its use as an anti-hormonal agent.

Another treatment used in the study is **Casodex-50**, which contains **bicalutamide** as the active ingredient. This medication is provided in the form of film-coated tablets, with each tablet containing 50 mg of the active substance. The administration route is **oral**, with a maximum daily dose of 50 mg and a total maximum dose of 18,000 mg over a 12-month period. Casodex-50 is produced by Laboratoires Juvisé Pharmaceuticals and is categorized under the ATC code L02BB03, also serving as an anti-hormonal treatment.

The experimental medication in the trial is **Avodart**, which contains **dutasteride** as the active substance. Avodart is available in the form of soft capsules, each containing 0.5 mg of dutasteride. The administration route is **oral**, with a maximum daily dose of 0.5 mg and a total maximum dose of 300 mg over a treatment period of 20 months. This product is manufactured by GlaxoSmithKline B.V. and is classified under the ATC code G04CB02, functioning as an anti-hormonal agent.

All medications in this trial are chemically derived and are not formulated for pediatric use. The trial aims to evaluate the efficacy of dutasteride in combination with combined androgen blockade therapy in patients with recurrent and/or metastatic salivary duct carcinoma. Compliance with dosing schedules and administration routes will be monitored throughout the study to ensure adherence to the protocol.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the **Overall Response Rate (ORR)**, which is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) as determined by the Investigator according to RECIST version 1.1. Additionally, the Duration of Response (DoR) will be evaluated, defined as the time from the first tumor assessment showing PR or CR, subsequently confirmed, until documented progressive disease (PD) or death from any cause, whichever occurs first.

Secondary endpoints will further assess efficacy through measures such as Progression Free Survival (PFS), Overall Survival (OS), and Clinical Benefit Rate (CBR). PFS is defined as the time from study enrollment until the first documented disease progression or death due to any cause. OS is measured from study enrollment to the date of death from any cause. CBR includes confirmed CR or PR at any time or stable disease (SD) of at least 6 months, as determined by the Investigator per RECIST v1.1.

Additional secondary endpoints include the incidence of serious adverse events (SAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, quality of life assessments using approved EORTC and VAS questionnaires, and various biomarker analyses. These biomarker analyses will include circulating tumor DNA (ctDNA), serum testosterone levels, AR and AR splice variants, SRD5A1/SRD5A2 mRNA expression on baseline and post-treatment tumor tissue samples, and various subsets of immune cells.