| Eligibility |
Inclusion Criteria:
1. Participant is a male = 18 years of age the time of signing the informed consent form
(ICF).
2. Histologically confirmed adenocarcinoma of the prostate.
3. Surgically or medically castrated, with testosterone levels of < 50 ng/dL (<2.0 nM).
If the participant is being treated with luteinizing hormone-releasing hormone (LHRH)
agonists/antagonists (participant who have not undergone orchiectomy) this therapy
must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued
throughout the study.
Participants must have failed prior therapy with enzalutamide or apalutamide
- Has completed at least 12 weeks of prior continuous therapy with enzalutamide or
apalutamide .
- Has been without enzalutamide, or apalutamide treatment for >30 days prior to
initiation of study treatment.
4. Documented prostate cancer progression as assessed by the investigator with one of the
following:
- Prostate-specific antigen (PSA) progression defined by a minimum of 3 rising PSA
levels with an interval of =1 week between each determination. The PSA value at
screening must be =1 µg/L (1 ng/mL) if PSA is the only indication of progression;
participants on systemic glucorticoids for control of symptoms must have
documented PSA progression by PCWG3 criteria while on systemic glucocorticoids
prior to commencing Cycle 1 Day 1 treatment.
- Radiographic progression of soft tissue disease by RECIST 1.1 or bone metastasis
with 2 or more documented new bone lesions on a bone scan with or without PSA
progression.
5. Participants must have FDHT lesion >2 cm lesion that has an SUVmax of 2.9 or less in
bone, or 2.4 or less in soft tissue, or two or more smaller lesions that meet those
criteria.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
7. Participants must have the following laboratory values:
- Absolute neutrophil count (ANC) = 1.5 x 109/L without growth factor support for 7
days (14 days if participant received pegfilgastrim)
- Hemoglobin (Hgb) = 9 g/dL (= 90 g/L or > 5.59 mmol/L)
- Platelet count (plt) = 100 x 109/L
- Serum potassium concentration within normal range, or correctable with
supplements
- Serum AST/SGOT and ALT/SGPT = 3.0 x Upper Limit of Normal (ULN) or = 5.0 x ULN if
liver metastases are present
- Serum total bilirubin = 1.5 x ULN (= 2 x ULN in case of documentened Gilbert).
- Participants must have serum albumin = 3.0 g/dL
- Serum creatinine = 1.5 x ULN, or measured glomerular filtration rate (GFR) = 60
mL/min/1.73m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr
EDTA or 125I iothalamate. In cases where the serum creatinine is < 1,5xULN, there
is no need to calculate GFR.
- PT (or INR) and activated partial thromboplastin time (APTT)
1. within normal range (Part A)
2. =1.5 ULN
Exclusion Criteria:
1. Participant has received anti-cancer therapy (either approved or investigational) < 4
weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
- < 42 days for prior nitrosureas or mitomycin C
2. Toxicities resulting from prior systemic cancer therapies must have resolved to = NCI
CTCAE Grade 1 prior to starting CC-90011 treatment (with exception of Grade 2
peripheral neuropathy and alopecia).
3. Previous anaphylactic reaction to either FDHT or FDG.
4. Participant has undergone major surgery = 4 weeks or minor surgery = 2 weeks prior to
Cycle 1 Day 1 or who have not recovered from surgery.
5. Participant has completed any radiation treatment < 4 weeks prior to Cycle 1 Day 1 or
< 2 weeks for palliative bone radiotherapy (single fraction). Participants with > 25%
of myelopoietic bone marrow radiation are not allowed to be enrolled on this study.
6. Participant has persistent diarrhea due to a malabsorptive syndrome (such as celiac
sprue or inflammatory bowel disease) = NCI CTCAE Grade 2, despite medical management),
or any other significant GI disorder that could affect the absorption of CC-90011.
7. Participant with symptomatic or uncontrolled ulcers (gastric or duodenal),
particularly those with a history of and/or risk of perforation and GI tract
hemorrhages.
8. Participant with any hemorrhage/bleeding event > CTCAE Grade 2 or haemoptysis > 1
teaspoon within 4 weeks prior to the first dose
9. Symptomatic and untreated or unstable central nervous system (CNS) metastases or
clinically significant spinal cord compression.
- Participant recently treated with whole brain radiation or stereotactic
radiosurgery for CNS metastases must have completed therapy at least 4 weeks
prior to Cycle 1, Day 1 and have a follow-up brain computed tomography (CT) or
magnetic resonance imaging (MRI) demonstrating either stable or improving
metastases 4 or more weeks after completion of radiotherapy (the latter to be
obtained as part of the Screening Assessments, refer to Section 6.1)
- Participant must be asymptomatic and off steroids or on stable dose of steroids
for at least 4 weeks (?10 mg/day prednisone equivalent)
10. Participant has known symptomatic acute or chronic pancreatitis.
11. Participant with severe hepatic impairment (Child-Pugh Class C).
12. Medical castration with LHRH analogue is not permitted at any time during treatment
with abiraterone and prednisone if not started at least 4 weeks prior to Cycle 2 Day
1.
13. Participant has impaired cardiac function or clinically significant cardiac diseases,
including any of the following considered to be clinically significant by the
subject's physician:
- LVEF < 45% as determined by multiple gated acquisition scan (MUGA) or
echocardiogram (ECHO)
- Complete left bundle branch or bifascicular block
- Congenital long QT syndrome
- Persistent or clinically meaningful ventricular arrhythmias or atrial
fibrillation.
- QTcF = 450 msec on Screening ECG (mean of triplicate recordings)
- Unstable angina pectoris or myocardial infarction = 6 months prior to starting
CC-90011
14. Participant has other clinically significant heart disease such as congestive heart
failure requiring treatment or uncontrolled hypertension (blood pressure ? 160/95 mm
Hg).
15. Participants who are known to be human immunodeficiency virus (HIV) positive with an
acquired immunodeficiency syndrome (AIDS) defining opportunistic infection within the
last year, a detectable viral load, or a current CD4 count < 350 cells/uL.
16. Participant has untreated chronic hepatitis B or chronic hepatitis B virus (HBV)
carriers with HBV DNA > 500 IU/mL (2500 copies/mL), or active hepatitis C. Inactive
hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA
< 500 IU/mL), and cured hepatitis C participants can be enrolled.
17. Participant with ongoing treatment with chronic, therapeutic dosing of anticoagulants
(eg, warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin
antagonist). Low dose low molecular weight heparin for catheter maintenance and for
short-term prophylaxis for participants with prior pulmonary embolism (PE) and deep
vein thrombosis (DVT) are permitted under careful consideration by the Investigator.
18. Participant has a history of concurrent second cancers requiring active, ongoing
systemic treatment.
19. Participant has any significant medical condition (eg, active or uncontrolled
infection or renal disease), the presence of laboratory abnormalities, or psychiatric
illness that would prevent the participant from participating (or compromise
compliance) in the study or would place the participant at unacceptable risk if he/she
were to participate in the study.
20. Participants with poor bone marrow reserve as assessed by Investigator such as in the
following conditions of:
- Having received extensive bone radiotherapy
- Having experienced several episodes of bone marrow aplasia in previous treatments
- Requiring regular hematopoietic support (blood transfusion, erythropoietin, GCSF)
21. Participant has any condition that confounds the ability to interpret data from the
study.
22. Participant does not tolerate the study drug components.
23. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20
days for severe/critical illness prior to Cycle 1 Day 1 (C1D1).
• Acute symptoms must have resolved and based on investigator assessment in
consultation with the Study Sponsor Physician, there are no sequelae that would place
the subject at a higher risk of receiving study treatment
24. Previous SARS-CoV-2 vaccine within 7 days of C1D1. For vaccines requiring more than
one dose, the full series (e.g. both doses of a two-dose series) should be completed
prior to C1D1 when feasible and when a delay in C1D1 would not put the study subject
at risk.
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