DUCT: Phase II Dutasteride in Combination With CAB vs CAB in SDC
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Combined androgen blockade (CAB) Patients from cohort A (ADT-naïve) may be randomized in this arm to receive CAB. |
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:
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:
|
| Experimental: Combined androgen blockade (CAB) + dutasteride 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. |
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:
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:
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:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [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) [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.
Secondary Outcome Measures
- 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]
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) [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.
- 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]
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 [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.
- 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]
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 [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.
- 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]
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 [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)
- Circulating tumor DNA (ctDNA) levels [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.
- mRNA expression levels of AR and AR splice variants [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)
- mRNA expression levels of SRD5A1/SRD5A2 [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)
Eligibility Criteria
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)
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Patients who do not have adequate swallowing capacity
-
Patients familiar with Long QT-syndrome (LQTS)
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Patients (M/F) with reproductive potential not implementing adequate contraceptive measures
-
Patients that are pregnant or lactating
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Patients with uncontrolled illness including:
-
Cardiovascular disorders, including symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
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Uncontrolled hypertension
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Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before inclusion
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Serious active infections
-
Patients undergoing concomitant treatments including:
-
Concomitant (or within 4 weeks before inclusion) administration of any other experimental drug under investigation
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Concomitant (or within 6 months before inclusion) administration of any 5-alpha reductase inhibitor, i.e. dutasteride or finasteride
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Radboudumc | Nijmegen | Gelderland | Netherlands | 6500HB |
Sponsors and Collaborators
- Radboud University Medical Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MOHN22