Clinical trial NCT05513365: Phase II Dutasteride in Combination With CAB vs CAB in SDC
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Salivary Duct Carcinoma
Keywords: Salivary duct carcinoma
Androgen deprivation therapy
Combined androgen blockade
Dutasteride
Goserelin
Bicalutamide
anti-androgens
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2022-08-24
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention 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.

Cohort A is closed for inclusion as of April 18, 2024.
Primary purpose: TREATMENT

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 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.

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.

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 (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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 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
measure: Duration of Response (DoR)
timeFrame: 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 outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Clinical benefit rate (CBR)
timeFrame: 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
measure: Overall survival (OS)
timeFrame: 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
measure: Quality of Life (QoL) based on the EORTC QLQ-C30 questionnaire
timeFrame: 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
measure: Quality of Life (QoL) based on the EORTC QLQ-H&N43 questionnaire
timeFrame: 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
measure: Quality of Life (QoL) based on the EORTC QLQ-SHQ22 questionnaire
timeFrame: 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
measure: Pain level assessed by the VAS (visual analog scale) questionnaire
timeFrame: 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
measure: Adverse Events according to CTCAE v5.0
timeFrame: 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
measure: Circulating tumor DNA (ctDNA) levels
timeFrame: through study completion, estimated after 3 years
measure: mRNA expression levels of AR and AR splice variants
timeFrame: through study completion, estimated after 3 years
measure: mRNA expression levels of SRD5A1/SRD5A2
timeFrame: through study completion, estimated after 3 years
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: C.M.L. van Herpen, prof. MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weijers JAM, Verhaegh GW, Lassche G, van Engen-van Grunsven ACH, Driessen CML, van Erp NP, Jonker MA, Schalken JA, van Herpen CML. A randomized phase II trial on the addition of dutasteride to combined androgen blockade therapy versus combined androgen blockade therapy alone in patients with advanced or metastatic salivary duct carcinoma - the DUCT study protocol. BMC Cancer. 2024 Sep 20;24(1):1174. doi: 10.1186/s12885-024-12889-0.