Clinical trial NCT02009332: Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer
Official title: A Combined Phase 1 and Phase 2 Study of Albumin-bound Rapamycin Nanoparticles (Nab-rapamycin, ABI-009) in the Treatment of BCG Refractory or Recurrent Nonmuscle Invasive Transitional Cell Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-muscle Invasive Bladder Cancer (NMIBC)
Lead sponsor: Aadi Bioscience, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-12-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The phase 1 dose-escalation portion used the 3+3 dose escalation rule. Initially 3 patients will be treated. If none develops DLT following the third weekly instillation, the dose can be escalated. If only 1 of the first 3 patients develops DLT, then an additional 3 patients will be treated at that dose. At any dose level, if 2 or more cases develop DLT, the prior dose will be defined as the MDD once 6 patients have been treated at this level with less than 2 patients experiencing a DLT.

In phase 2, up to 29 patients will receive intravesical ABI-009 and gemcitabine using the Simon 2-stage design: initially, there will be only 10 patients enrolled with a rejection rule that only if there are 2 or more positive responses will the study proceed to further enrollment of the next 19 patients.
Primary purpose: TREATMENT

Brief summary: Purpose of this study is to determine appropriate dosing of ABI-009 and evaluate the safety and anti-tumor activity of ABI-009 in treatment of non-muscle invasive bladder cancer


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Dose Limiting Toxicities (DLT) Following Intravesical Administration of ABI-009
timeFrame: Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months)
measure: Phase 2: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 and Gemcitabine
timeFrame: End of Study [EOS, 3 months]
Secondary outcomes:
measure: Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009
timeFrame: End of Study [EOS, 3 months]
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Columbia University
name: James McKiernan, MD
role: PRINCIPAL_INVESTIGATOR
References: