Phase II Dutasteride in combination with CAB vs CAB in SDC (DUCT)

Phase 2/3

Recruiting

• Conditions: Salivary Duct Carcinoma

• Registration Number: 2022-500745-24-00
• Lead Sponsor: Stichting Radboud University Medical Center

Brief Summary

To determine the efficacy of dutasteride in combination with combined androgen blockade therapy in patients with recurrent and/or metastatic salivary duct carcinoma

Detailed Description

Not available

Study Timeline

• Study First Posted: 2022-08-11
• Last Update Posted: 2024-04-18

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 26

Inclusion Criteria

Pathologically/histologically proven diagnosis of (incurable) AR+ R/M salivary duct carcinoma

Adequate cardiac function

AR positive diseases (strong expression in at least 1% of nuclei of neoplastic cells based on central IHC review)

Measurable disease per RECIST version 1.1 at baseline

Age ≥ 18 years

Written informed consent must be given according to national/local regulation

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Adequate bone marrow function: (WBC ≥ 3.5x10^9 /L; Absolute neutrophil count (ANC) ≥ 1.5x10^9/L; Hemoglobin ≥ 6.20 mmol/L; Platelet count ≥ 100x10^9/L)

Adequate liver function: (Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) OR ≤ 5.0 times ULN for patients with liver metastases; Bilirubin ≤ 1.5 times ULN. For patients known with Gilbert’s Syndrome ≤ 3.0 times ULN is permitted)

Adequate renal function: (Serum creatinine level ≤ 1.5 times ULN or calculated creatinine clearance ≥ 30 mL/min based on CKD-EPI-GFR)

Exclusion Criteria

Patients with history of allergic reactions attributed to compounds of similar chemical or biological composition to goserelin, bicalutamide or dutasteride

Concurrent treatment with any other anti-cancer therapy within the last 4 weeks before inclusion

Curative radiation therapy within the last 4 weeks before inclusion or palliative radiation therapy 1 week before start of study

Any condition which, in the opinion of the investigator, would preclude participation in this clinical study

Patients with peanut or soy allergy (dutasteride capsules contain lecithin which may contain soy oil)

Patients who do not have adequate swallowing capacity

Patients familiar with Long QT-syndrome (LQTS)

Patients (M/F) with reproductive potential not implementing adequate contraceptive measures

Patients that are pregnant or lactating

Patients with uncontrolled illness including: Cardiovascular disorders, including symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias; Uncontrolled hypertension (defined as sustained systolic BP > 160 mm Hg, or diastolic BP > 100 mm Hg. Unless evidence of white-coat hypertension), Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before inclusion; Serious active infections .

Concomitant (or within 4 weeks before inclusion) administration of any other experimental drug under investigation

Concomitant (or within 6 months before inclusion) administration of any 5-alpha reductase inhibitor, i.e. dutasteride or finasteride

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) determined by Investigator according to RECIST v1.1		Overall response rate (ORR) defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) determined by Investigator according to RECIST v1.1
Duration of Response (DoR), defined as the time from first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed until documented progressive disease (PD) determined by Investigator per RECIST v1.1 or death from any cause, whichever occurs first		Duration of Response (DoR), defined as the time from first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed until documented progressive disease (PD) determined by Investigator per RECIST v1.1 or death from any cause, whichever occurs first

Secondary Outcome Measures

Name	Time	Method
AR, AR splice variants and SRD5A1/SRD5A2 mRNA expression on baseline and post-treatment tumor tissue samples		AR, AR splice variants and SRD5A1/SRD5A2 mRNA expression on baseline and post-treatment tumor tissue samples
Quality of life (QoL) assessments according to approved EORTC (QLQ-C30, QLQ-H&N35, QLQ-SHQ22) and VAS questionnaires		Quality of life (QoL) assessments according to approved EORTC (QLQ-C30, QLQ-H&N35, QLQ-SHQ22) and VAS questionnaires
Circulating tumor DNA (ctDNA) and serum testosterone		Circulating tumor DNA (ctDNA) and serum testosterone
Progression free survival (PFS), defined as the time from study enrolment until the date of first documented disease progression by Investigator as per RECIST v1.1, or death due to any cause, whichever occurs first		Progression free survival (PFS), defined as the time from study enrolment until the date of first documented disease progression by Investigator as per RECIST v1.1, or death due to any cause, whichever occurs first
Overall survival (OS), defined as the time from study enrolment to the date of death due to any cause		Overall survival (OS), defined as the time from study enrolment to the date of death due to any cause
Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator as per RECIST v1.1		Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator as per RECIST v1.1
Incidence of SAE’s according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.		Incidence of SAE’s according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Various subsets of immune cells. Including different panels, but not limited to, a lymphocyte panel, a dendritic cell panel, a checkpoint panel, and a myeloid-derived suppressor cell panel		Various subsets of immune cells. Including different panels, but not limited to, a lymphocyte panel, a dendritic cell panel, a checkpoint panel, and a myeloid-derived suppressor cell panel

Trial Locations

Locations (1)

Stichting Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands

Stichting Radboud University Medical Center

🇳🇱Nijmegen, Netherlands

Carla van Herpen

Site contact

+31243614038

Carla.vanHerpen@radboudumc.nl