A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer

Phase 1

Active, not recruiting

• Conditions: Metastatic Castration-resistant Prostate Cancer; MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-001305-23-NL
• Lead Sponsor: Amgen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-30
• Last Update Posted: 1 February 2022

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Male
• Target Recruitment: 105

Inclusion Criteria

All Subprotocols
- Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without pure neuroendocrine differentiation or small cell features
- Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist.
- Total serum testosterone should be = 50 ng/dL (or 1.7 nmol/L)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 1
- Life expectancy of > 3 months
- Adequate organ function, defined as follows:
• absolute neutrophil count = 1.5 x 10^9/L (without growth factor support within 7 days from screening assessment)
• platelet count = 100 x 10^9/L (without platelet transfusion within 7 days from screening assessment)
• hemoglobin > 9 g/dL (90 g/L) (subprotocol A) / > 10 g/dL (100g/L) (subprotocol B) (without blood transfusion within 7 days from screening assessment)
• estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation = 30 mL/min/1.73 m2
• AST and ALT < 3 x upper limit of normal (ULN) (or < 5 x ULN for subjects with liver involvement)
• total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for subjects with liver metastases)
• left ventricular ejection fraction (LVEF)> 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available)
- Baseline electrocardiogram (ECG) QTc = 470 msec

Subprotocol A & B only
- Subjects planning to receive enzalutamide (subprotocol A) / abiraterone (subprotocol B) for the first time for mCRPC (subjects who received prior enzalutamide (subprotocol A) / abiraterone (subprotocol B) are not eligible).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 53
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion Criteria

All Subprotocols
- Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma
- CNS metastases or leptomeningeal disease
- Symptomatic peripheral sensory or motor neuropathy =grade 3
- History or presence of clinically relevant CNS pathology
- Confirmed history/current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
- Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials within 7 days of dosing
- History/evidence of inflammatory bowel disease or any other GI disorder causing chronic nausea, vomiting, or diarrhea
- History of arterial or venous thrombosis within 12 months of first dose
- Myocardial infarction, uncontrolled hypertension (Subprotocol A), unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 160
- Unresolved toxicities from prior anti-tumor therapy not having resolved to CTCAE version 5.0 grade 1, with the exception of alopecia or toxicities that are stable and well-controlled AND there is agreement to allow by both the investigator and sponsor
- Known HIV infection, hepatitis C or hepatitis B infection
- History of other malignancy within the past 2 years, with the following exceptions:
• Malignancy treated with curative intent and with no known active disease present for = 3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
- Prior treatment with a taxane for mCRPC.
- Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks)
- Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including LHRH/GnRH analogue. Subjects on a stable bisphosphonate or denosumab regimen for = 30 days prior to enrollment are eligible
- Prior PSMAxCD3 bispecific therapy
- Requiring chronic systemic corticosteroid therapy or any other immunosuppressive therapies. Low dose corticosteroids permitted.
- Prior major surgery within 4 weeks of first dose
- Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies).
- Male subjects with a female partner of childbearing potential or pregnant partner who are unwilling to practice sexual abstinence or use contraception during treatment and for an additional 4 months after the last dose
- Male subjects unwilling to abstain from donating sperm during treatment and for an additional 4 months after the last dose.
- Subject has known sensitivity to any of the products (or components) to be administered during dosing.
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified