Phase II Dutasteride in Combination With CAB vs CAB in SDC (DUCT)

April 22, 2024 updated by: Radboud University Medical Center

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

Phase 2 clinical trial on the addition of dutasteride to combined androgen blockade (CAB) therapy in recurrent and/or metastatic (R/M) salivary duct carcinoma (SDC) patients.

The study included two cohorts of patients: Cohort A, which comprises ADT-naïve patients, and Cohort B, which comprises ADT-resistant patients.

Cohort A is closed for inclusion as of April 18, 2024.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A prospective, randomized controlled, single-institution, phase II clinical trial to assess the objective response rate (ORR), duration of response (DoR), progression free survival (PFS), overall survival (OS), toxicity, quality of life (QoL), and expression of molecular targets of patients with R/M SDC treated with either combined androgen blockade (CAB; goserelin + bicalutamide) or CAB + dutasteride, Participants in Cohort A will be randomized 1:1 at the study entry to receive CAB (goserelin 10.8 mg/3months + bicalutamide 50 mg/once daily) or CAB + dutasteride (0.5 mg/once daily). Participants will receive treatment until until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.

Cohort A is closed for inclusion as of April 18, 2024.

Study Type

Interventional

Enrollment (Estimated)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500HB
        • Recruiting
        • Radboudumc
        • Principal Investigator:
          • Carla ML van Herpen, MD, PhD
        • Contact:
        • Sub-Investigator:
          • Jetty AM Weijers, MSc
        • Sub-Investigator:
          • Jack A Schalken, PhD
        • Sub-Investigator:
          • Gerald W Verhaegh, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically/histologically proven diagnosis of (incurable) AR+ R/M salivary duct carcinoma
  • 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. Appendix II.
  • 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 (Appendix III).
  • Adequate bone marrow function:
  • WBC ≥ 3.5/10^9 /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
  • Adequate cardiac function

Exclusion Criteria:

  • Patients with history of allergic reactions attributed to compounds of similar chemical or biological composition to goserelin, bicalutamide or dutasteride
  • 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
  • Patients undergoing concomitant treatments including:
  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined androgen blockade (CAB) + dutasteride
Patients from cohort B (ADT-resistant) will receive CAB+dutasteride.
Drug: Goserelin 10.8 mg
Goserelin injection (10.8 mg) once per 3 months until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.
Other Names:
  • Zoladex
Drug: Bicalutamide 50 mg
Bicalutamide tablets (50 mg) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.
Other Names:
  • Casodex
Drug: Dutasteride 0.5 mg
Dutasteride capsules (0.5 mg) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.
Other Names:
  • Avodart

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Response will be measured according to RECIST version 1.1, the ORR is defined as the sum of the complete remissions plus partial responses. The best response will be used in each patient.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Duration of Response (DoR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Response will be measured according to RECIST version 1.1, the DoR is defined as the time from first tumor assessment at which the overall response was recorded as partial response (PR) or complete response (CR) that is subsequently confirmed until documented progressive disease (PD) or death form any cause, whichever occurs first.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Response will be measured according to RECIST version 1.1, the PFS is defined as the time from study enrolment until date of first documented disease progression or death due to any cause, whichever occurs first.Every 12 weeks a CT/MRI scan will be made to asses the progression free survival until PD.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Clinical benefit rate (CBR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Response will be measured according to RECIST version 1.1, the CBR is defined as the confirmed CR or PR at any time or stable disease (SD) of at least 6 months. Every 12 weeks a CT/MRI scan will be made to asses the clinical benefit rate until PD.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Overall survival (OS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
The OS is defined as the time from study enrolment to the date of death to any cause.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Quality of Life (QoL) based on the EORTC QLQ-C30 questionnaire
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Quality of Life (QoL) based on the EORTC QLQ-C30 questionnaire. Participants are asked to fill in the questionnaires in week 0 (before start of treatment, baseline), every 12 weeks, and at PD.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Quality of Life (QoL) based on the EORTC QLQ-H&N43 questionnaire
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Quality of Life (QoL) based on the EORTC QLQ-H&N43 questionnaire. Participants are asked to fill in the questionnaires in week 0 (before start of treatment, baseline), every 12 weeks, and at PD.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Quality of Life (QoL) based on the EORTC QLQ-SHQ22 questionnaire
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Quality of Life (QoL) based on the EORTC QLQ-SHQ22 questionnaire. Participants are asked to fill in the questionnaires in week 0 (before start of treatment, baseline), every 12 weeks, and at PD.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Pain level assessed by the VAS (visual analog scale) questionnaire
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Scale range 0-10, in which a higher score represents more pain. Participants are asked to fill in the questionnaires in week 0 (before start of treatment, baseline), every 12 weeks, and at PD.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Adverse Events according to CTCAE v5.0
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Adverse events will be recorded using International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, the investigator will assess whether those events are drug related. Every OPD visit (every 3 months until PD)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Circulating tumor DNA (ctDNA) levels
Time Frame: through study completion, estimated after 3 years
ctDNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted. Baseline, 3 months, 6 months, and at PD.
through study completion, estimated after 3 years
mRNA expression levels of AR and AR splice variants
Time Frame: through study completion, estimated after 3 years
mRNA expression of AR and AR splice variants on baseline and post-treatment tumor tissue samples to evaluate whether treatment response and disease progression can be predicted. Pre-treatment and post-treatment (i.e. PD)
through study completion, estimated after 3 years
mRNA expression levels of SRD5A1/SRD5A2
Time Frame: through study completion, estimated after 3 years
mRNA expression of SRD5A1/SRD5A2 on baseline and post-treatment tumor tissue samples to evaluate whether treatment response and disease progression can be predicted. Pre-treatment and post-treatment (i.e. PD)
through study completion, estimated after 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

  • Principal Investigator: Carla van Herpen, MD, PhD, Radboud University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 27, 2022

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

August 18, 2022

First Submitted That Met QC Criteria

August 23, 2022

First Posted (Actual)

August 24, 2022

Study Record Updates

Last Update Posted (Actual)

April 24, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MOHN22
  • 1140022110057 (Other Grant/Funding Number: ZonMw)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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