prostaat kanker Metastatic Castration-Resistant Prostate Cancer
Conditions
Interventions
None listed
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: All parts - Age >= 18 years at the time of signing the informed consent - Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting. - Expansion cohort 1b only: maximum of 3 systemic therapies administered in any prostate cancer disease setting (including chemotherapy, systemic radiotherapy, novel hormonal, or investigational therapies, but not including ADT or bone targeted therapies) - Expansion cohort 1b only: subjects with baseline PSMA-positive disease assessed by PSMA PET scan (central assessment) - Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist - Total serum testosterone = 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart • nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications • appearance of 2 or more new lesions in bone scan - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Please see section 6.1 of the protocol.
Exclusion criteria
Exclusion criteria: All parts - Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma - Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose) - Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression - Prior major surgery within 4 weeks of first dose - Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study - Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management within 7 days of dosing NOTE: Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with sponsor. Screening for chronic infectious conditions is not required. - History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism or deep vein trombosis) within 12 months of first dose of AMG 160 - Symptomatic peripheral sensory or motor neuropathy of grade >= 3 - History or presence of clinically relevant CNS pathology as uncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis - Myocardial infarction, unstable angina, cardia 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 Common Terminology Criteria for Adverse Events (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 - History of other malignancy within the past 2 years, with the following exception(s): • malignancy treated with curative intent and with no known active disease present for >= 2 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 - History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease) or any other gastrointestinal disorder causing chronic nausea, vomiting, or diarrhea (defined as >= 2 CTCAE grade 2) - Prior PSMA-targeted therapy (subjects on prior PSMA radionuclide therapy may be eligible if discussed with Amgen medical monitor prior to enrollment) NOTE: subject cannot have received PSMA radionuclide therapy = 30 days prior to enrollment are eligible - Needing chronic systemic corticosteroid therapy (prednisone dose > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-TNFa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint • dose-limiting toxicities (DLTs) • treatment-emergent adverse events • treatment-related adverse events • changes in vital signs, electrocardiogram (ECG), and clinical laboratory tests | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters/outcome of the study (if applicable): • PK parameters for AMG 160 following IV administration including but not limited to maximum serum concentration (Cmax), minimum serum concentration (Cmin), area under the concentration-time curve (AUC) over the dosing interval, accumulation following multiple dosing, and, if feasible, half-life (t1/2) • objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications • prostate-specific antigen (PSA) response • duration of response (DOR) (radiographic and PSA) • 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography(PET)/computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET/CT based response evaluation (Parts 4 and 5 are not included) • time to progression (radiographic and PSA) • progression-free survival (PFS) (radiographic and PSA) • 1, 2, and 3-year overall survival (OS) • circulating tumor cells (CTCs) - response (CTC0) and rate of CTC conversion • other PCWG3-recommended endpoints (time to symptomatic skeletal events, alkaline phosphatase [total, bone], lactate dehydrogenase [LDH], hemoglobin, neutrophil-to-lymphocyte ratio, urine N-telopeptide) • PK parameters of specific probes of CYP enzymes including, but not limited to, Cmax, area under the concentration-time curve over a 24 hour period (AUC24) and, if feasible, t1/2 Please see protocol section 4 for more information. | — |
Countries
Netherlands
Outcome results
None listed