| Eligibility |
Inclusion Criteria:
1. Patient is male or female aged =18 years.
2. Patient provided signed and dated informed consent prior to initiation of any study
procedures.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0
(fully active, able to carry out all pre-disease activities without restriction) or 1
(unable to perform physically strenuous activity but ambulatory and able to carry out
work of a light or sedentary nature).
4. Patient has a predicted life expectancy of =3 months.
5. Patient has a GFR of =30 mL/min/1.73 m^2.
6. Patient has adequate hepatic function, as evidenced by a total bilirubin =1.5 × ULN,
aspartate transaminase (AST), and /or alanine transaminase (ALT) =3 × ULN or =5 ×ULN,
if due to liver involvement by tumor.
7. Patient has adequate bone marrow function, as evidenced by hemoglobin =9.0 g/dL in the
absence of transfusion within the previous 72 hours, platelet count =100×10^9cells/L,
and absolute neutrophil count (ANC) =1.5×10^9 cells/L.
8. Patient has no significant ischemic heart disease or myocardial infarction (MI) within
6 months before the first dose of CPX-POM and currently has adequate cardiac function,
as evidenced by a left ventricular ejection fraction of >50% as assessed by
multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and corrected QT
interval (QTc) <470 msec by Fridericia (QTcF). The eligibility of patients with
ventricular pacemakers for whom the QT interval may not be accurately measurable will
be determined on a case by-case basis by the Sponsor in consultation with the Medical
Monitor.
9. Patient and his/her partner agree to use adequate contraception after providing
written informed consent through 3 months after the last dose of CPX-POM, as follows:
1. For women: Negative pregnancy test during Screening and at Day 1 of each
treatment cycle and compliant with a medically approved contraceptive regimen
during and for 3 months after the treatment period or documented to be surgically
sterile or postmenopausal.
2. For men: Compliant with a medically-approved contraceptive regimen during and for
3 months after the treatment period or documented to be surgically sterile. Men
whose sexual partners are of child-bearing potential must agree to use 2 methods
of contraception prior to study entry, during the study, and for 3 months after
the treatment period.
10. Patient is willing and able to participate in the study and comply with all study
requirements.
11. Patients must have histologically confirmed MIBC (=T2, N0-N1, M0 per AJCC) pure or
mixed histology urothelial carcinoma. Clinical node-positive (N1) patients are
eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within
the planned surgical LN dissection template.
12. The initial TURBT that showed muscularis propria invasion should be within 8 weeks
prior to beginning study therapy, when feasible. There must be adequate evaluable
tumor burden in the tissue blocks (from initial or repeat TURBT with highest tumor
content) to allow for analysis as determined by the local site pathologist.
13. Patients must be ineligible for cisplatin-based chemotherapy due to any of the
following:
1. Creatinine clearance(CrCl) <60 mL/min with Eastern Cooperative Oncology Group
(ECOG) Performance Status (PS) 0-1
2. Hearing impaired = Grade 2 by CTCAE criteria
3. Neuropathy = Grade 2 by CTCAE criteria
4. Heart failure New York Heart Association (NYHA) = III
Exclusion Criteria:
Patients who meet any of the following exclusion criteria are not to be enrolled in the
Expansion Cohort.
1. Baseline GFR <30 mL/min/1.73 m^2.
2. Women must not be pregnant or breastfeeding since we do not know the effects of
CPX-POM on the fetus or breastfeeding child.
3. Patients may not have concurrent upper urinary tract (i.e. ureter, renal pelvis)
invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper
tract urothelial carcinoma that has been definitively treated with at least one
post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates
no evidence of residual disease are eligible.
4. Patients may not have another malignancy that could interfere with the evaluation of
safety or efficacy of the study drugs. Patients with a prior malignancy will be
allowed without study chair approval in the following circumstances:
1. Not currently active and diagnosed at least 3 years prior to the date of
registration.
2. Non-invasive diseases such as low risk cervical cancer or any cancer in situ.
3. Localized (early stage) cancer treated with curative intent (without evidence of
recurrence and intent for further therapy), and in which no chemotherapy was
indicated.( (e.g. low/ intermediate risk prostate cancer, etc.).
5. Patients may not have undergone major surgery with the exception of TURBT (e.g.
intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic
injury or specific anti-cancer treatment = 4 weeks prior to starting study drug, or
patients who have had percutaneous biopsies or placement of vascular access device = 1
week prior to starting study drug, or who have not recovered from side effects of such
procedure or injury.
6. Patients must not have clinically significant cardiac disease.
7. Patients may not have chronic active liver disease or evidence of acute or chronic
Hepatitis B Virus (HBV) or Hepatitis C (HCV).
8. Patients may not have known diagnosis of human immunodeficiency virus (HIV) infection.
Testing is not required in absence of clinical suspicion.
9. Patients may not have known diagnosis of any condition (e.g. post hematopoietic or
solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires
chronic immunosuppressive therapy. Usage of non-steroidal anti-inflammatory
medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis
inhibitors for the treatment of gout are permitted.
10. Patients with any serious and/or uncontrolled concurrent medical conditions (e.g..,
active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that
could, in the investigator's opinion, cause unacceptable safety risks or potentially
interfere with the completion of the treatment according to the protocol are not
eligible.
11. Patients may not have any live viral vaccine used for prevention of infectious
diseases within 4 weeks prior to study drug(s).
12. Patients unwilling or unable to comply with the protocol.
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