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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Combined androgen blockade (CAB) + dutasteride
Patients from cohort B (ADT-resistant) will receive CAB+dutasteride.
干预措施: Goserelin 10.8 mg (Drug)
Combined androgen blockade (CAB) + dutasteride
Patients from cohort B (ADT-resistant) will receive CAB+dutasteride.
干预措施: Bicalutamide 50 mg (Drug)
Combined androgen blockade (CAB) + dutasteride
Patients from cohort B (ADT-resistant) will receive CAB+dutasteride.
干预措施: Dutasteride 0.5 mg (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 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.
Duration of Response (DoR)
时间窗: 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.
次要结局
- Quality of Life (QoL) based on the EORTC QLQ-SHQ22 questionnaire(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(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(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(through study completion, estimated after 3 years)
- mRNA expression levels of AR and AR splice variants(through study completion, estimated after 3 years)
- mRNA expression levels of SRD5A1/SRD5A2(through study completion, estimated after 3 years)
- Clinical benefit rate (CBR)(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)(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(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)
- Progression Free Survival (PFS)(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(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)