Phase II Dutasteride in Combination With CAB vs CAB in SDC

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат Bicalutamide 50 mg
  Bicalutamide tablets (50 mg) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.
• Препарат Dutasteride 0.5 mg
  Dutasteride capsules (0.5 mg) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw.

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: 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) [Срок оценки: 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]

Вторичные конечные точки (11)

• Progression Free Survival (PFS) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: through study completion, estimated after 3 years]
• mRNA expression levels of AR and AR splice variants [Срок оценки: through study completion, estimated after 3 years]
• mRNA expression levels of SRD5A1/SRD5A2 [Срок оценки: through study completion, estimated after 3 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Radboudumc — Nijmegen

Публикации

• 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):117 PMID 39304797

Идентификаторы

NCT: NCT05513365 · MOHN22 · 1140022110057

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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