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

Primary Purpose

Salivary Duct Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

Goserelin 10.8 mg

Bicalutamide 50 mg

Dutasteride 0.5 mg

About this trial

This is an interventional treatment trial for Salivary Duct Carcinoma focused on measuring Salivary duct carcinoma, Androgen deprivation therapy, Combined androgen blockade, Dutasteride, Goserelin, Bicalutamide, anti-androgens

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
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

Sites / Locations

RadboudumcRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Combined androgen blockade (CAB)

Combined androgen blockade (CAB) + dutasteride

Arm Description

Patients from cohort A (ADT-naïve) may be randomized in this arm to receive CAB.

Patients from cohort A (ADT-naïve) may be randomized in this arm to receive CAB+dutasteride, and patients from cohort B (ADT-resistant) will receive CAB+dutasteride without having been randomized.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)

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.

Duration of Response (DoR)

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.

Secondary Outcome Measures

Progression Free Survival (PFS)

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.

Clinical benefit rate (CBR)

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.

Overall survival (OS)

The OS is defined as the time from study enrolment to the date of death to any cause.

Quality of Life (QoL) based on the EORTC QLQ-C30 questionnaire

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.

Quality of Life (QoL) based on the EORTC QLQ-H&N43 questionnaire

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.

Quality of Life (QoL) based on the EORTC QLQ-SHQ22 questionnaire

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.

Pain level assessed by the VAS (visual analog scale) questionnaire

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.

Adverse Events according to CTCAE v5.0

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)

Circulating tumor DNA (ctDNA) levels

ctDNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted. Baseline, 3 months, 6 months, and at PD.

mRNA expression levels of AR and AR splice variants

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)

mRNA expression levels of SRD5A1/SRD5A2

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)

Full Information

NCT ID

NCT05513365

First Posted

August 18, 2022

Last Updated

March 29, 2023

Sponsor

Radboud University Medical Center

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT05513365

Brief Title

Phase II Dutasteride in Combination With CAB vs CAB in SDC

Acronym

DUCT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 27, 2022 (Actual)

Primary Completion Date

September 2025 (Anticipated)

Study Completion Date

September 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radboud University Medical Center

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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 will include two cohorts of patients: Cohort A, which comprises ADT-naïve patients, and Cohort B, which comprises ADT-resistant patients.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Salivary Duct Carcinoma

Keywords

Salivary duct carcinoma, Androgen deprivation therapy, Combined androgen blockade, Dutasteride, Goserelin, Bicalutamide, anti-androgens

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Patients will be included into two cohorts based on their previous treatments, either ADT-naïve (cohort A) or ADT-resistant patients (cohort B). In cohort A, the randomization will result in the allocation of the control arm (goserelin and bicalutamide) and experimental arm (goserelin, bicalutamide, and dutasteride) in a 1:1 ratio. In cohort B, patients ADT-resistant will be enrolled receiving similar therapy to the experimental arm, i.e. goserelin, bicalutamide, and dutasteride.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

98 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Combined androgen blockade (CAB)

Arm Type

Active Comparator

Arm Description

Patients from cohort A (ADT-naïve) may be randomized in this arm to receive CAB.

Arm Title

Combined androgen blockade (CAB) + dutasteride

Arm Type

Experimental

Arm Description

Patients from cohort A (ADT-naïve) may be randomized in this arm to receive CAB+dutasteride, and patients from cohort B (ADT-resistant) will receive CAB+dutasteride without having been randomized.

Intervention Type

Drug

Intervention Name(s)

Goserelin 10.8 mg

Other Intervention Name(s)

Zoladex

Intervention Description

Goserelin injection (10.8 mg) once per 3 months until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.

Intervention Type

Drug

Intervention Name(s)

Bicalutamide 50 mg

Other Intervention Name(s)

Casodex

Intervention Description

Bicalutamide tablets (50 mg) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.

Intervention Type

Drug

Intervention Name(s)

Dutasteride 0.5 mg

Other Intervention Name(s)

Avodart

Intervention Description

Dutasteride capsules (0.5 mg) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.

Primary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

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.

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

Title

Duration of Response (DoR)

Description

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

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

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

Title

Clinical benefit rate (CBR)

Description

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

Title

Overall survival (OS)

Description

The OS is defined as the time from study enrolment to the date of death to any cause.

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

Title

Quality of Life (QoL) based on the EORTC QLQ-C30 questionnaire

Description

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.

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

Title

Quality of Life (QoL) based on the EORTC QLQ-H&N43 questionnaire

Description

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.

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

Title

Quality of Life (QoL) based on the EORTC QLQ-SHQ22 questionnaire

Description

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.

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

Title

Pain level assessed by the VAS (visual analog scale) questionnaire

Description

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.

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

Title

Adverse Events according to CTCAE v5.0

Description

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

Title

Circulating tumor DNA (ctDNA) levels

Description

ctDNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted. Baseline, 3 months, 6 months, and at PD.

Time Frame

through study completion, estimated after 3 years

Title

mRNA expression levels of AR and AR splice variants

Description

Time Frame

through study completion, estimated after 3 years

Title

mRNA expression levels of SRD5A1/SRD5A2

Description

Time Frame

through study completion, estimated after 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carla van Herpen, MD, PhD

Organizational Affiliation

Radboud University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Radboudumc

City

Nijmegen

State/Province

Gelderland

ZIP/Postal Code

6500HB

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jetty AM Weijers, MSc

Phone

+31243611111

Jetty.Weijers@radboudumc.nl

First Name & Middle Initial & Last Name & Degree

Carla ML van Herpen, MD, PhD

First Name & Middle Initial & Last Name & Degree

Jetty AM Weijers, MSc

First Name & Middle Initial & Last Name & Degree

Jack A Schalken, PhD

First Name & Middle Initial & Last Name & Degree

Gerald W Verhaegh, PhD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Phase II Dutasteride in Combination With CAB vs CAB in SDC

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