A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC);-Subprotocol A: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 160 in Combination With Enzalutamide in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC) -Subprotocol B: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 160 in Combination With Abiraterone in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC)
- Conditions
- prostaat kankerMetastatic Castration-resistantprostate cancer10036958
- Registration Number
- NL-OMON54909
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 6
- Subject has provided informed consent prior to initiation of any study
specific activities/procedures.
- Age * 18 years at the time of signing the informed consent.
- 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
- 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).
Applicable for both 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 gastrointestinal
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.
Subprotocol A
- Use of strong CYP2C8 inhibitors within 7 days prior to first dose or strong
CYP3A4 induc
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The following primary study outcome is applicable for both combination<br /><br>therapies:<br /><br>To evaluate the safety, tolerability, and maximum tolerated dose (MTD) or<br /><br>recommended phase 2 dose (RP2D) of AMG 160 in combination with enzalutamide or<br /><br>abiraterone in subjects with metastatic castration-resistant prostate cancer<br /><br>(mCRPC)<br /><br>* dose-limiting toxicities (DLTs)<br /><br>* treatment-emergent and treatment-related adverse events<br /><br>* changes in vital signs and clinical laboratory tests</p><br>
- Secondary Outcome Measures
Name Time Method