Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer

Inclusion Criteria:

1. Patients must have a diagnosis of transitional cell carcinoma (TCC) of the urinary
bladder confirmed at the study institution. The patient must have demonstrated
nonmuscle-invasive bladder cancer refractory or recurrent to standard intravesical
therapy. Refractory disease is defined as failure to achieve tumor-free status by 6
months of initiation of adequate BCG therapy. Recurrent disease is defined as
reappearance of disease after achieving a tumor-free status by 6 months of initiation
of adequate BCG therapy. Adequate BCG therapy includes at least 6 weeks induction plus
3 additional doses of either induction or maintenance. Patients with a history of
other intravesical agents (except nab-rapamycin or gemcitabine) in addition to
standard BCG will also be allowed to enroll. All grossly visible disease must be fully
resected and pathologic stage will be confirmed at the institution where the patient
is enrolled. This will include stage Ta, T1, Tis and exclude all patients with muscle
invasion (T2).

1. For phase 1, patients with multifocal low-grade Ta histology will be eligible for
participation

2. For phase 2, individuals with Ta disease only must have documentation of
high-grade histology

3. For phase 2, prior intravesical treatment with nab-rapamycin or gemcitabine is
not allowed

2. Age >18 and must be able to read, understand, and sign informed consent

3. Performance Status: ECOG 0, 1, and 2 (See Appendix III)

4. Hematologic inclusion within 2 weeks of start of treatment

1. Absolute neutrophil count >1,500/mm3

2. Hemoglobin >9.0 g/dl

3. Platelet count >100,000/mm3

5. Hepatic inclusion within 2 weeks of entry

1. Total bilirubin must be within normal limits.

2. Adequate renal function with serum creatinine ≤2.5 mg/dL

3. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN for the
institution, alkaline phosphatase ≤ 2.5 x ULN for the institution, unless bone
metastasis is present in the absence of liver metastasis

6. Women of childbearing potential must have a negative pregnancy test.

7. All patients of childbearing potential must be willing to consent to using effective
contraception, ie, intrauterine device, birth control pills, depo-provera, and condoms
while on treatment and for 3 months after their participation in the study ends.

Exclusion Criteria:

1. Any other malignancy diagnosed within 1 year of study entry (except basal or squamous
cell skin cancers or noninvasive cancer of the cervix) is excluded

2. Concurrent treatment with any chemotherapeutic agent

3. Women who are pregnant or lactating

4. History of vesicoureteral reflux or an indwelling urinary stent

5. Participation in any other research protocol involving administration of an
investigational agent within 1 month prior to study entry

6. History of radiation to the pelvis

7. History of interstitial lung disease and/or pneumonitis

8. Evidence of metastatic disease