Title
Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer
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
Phase
Phase 1/Phase 2Lead Sponsor
Aadi, LLCStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Non-muscle Invasive Bladder Cancer (NMIBC)Intervention/Treatment
rapamycin ...Study Participants
21Purpose 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
ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.
Gemcitabine is administered after ABI-009 in the Phase 2 study.
Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks
Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks
Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks
Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks
Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks
ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 1 hour, once per week for 6 weeks; Gemcitabine, 2000 mg in 100 mL saline, administered intravesically after voiding of ABI-009 and retained for 1 hour, once per week for 6 weeks
Inclusion Criteria: 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). For phase 1, patients with multifocal low-grade Ta histology will be eligible for participation For phase 2, individuals with Ta disease only must have documentation of high-grade histology For phase 2, prior intravesical treatment with nab-rapamycin or gemcitabine is not allowed Age >18 and must be able to read, understand, and sign informed consent Performance Status: ECOG 0, 1, and 2 (See Appendix III) Hematologic inclusion within 2 weeks of start of treatment Absolute neutrophil count >1,500/mm3 Hemoglobin >9.0 g/dl Platelet count >100,000/mm3 Hepatic inclusion within 2 weeks of entry Total bilirubin must be within normal limits. Adequate renal function with serum creatinine ≤2.5 mg/dL 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 Women of childbearing potential must have a negative pregnancy test. 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: 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 Concurrent treatment with any chemotherapeutic agent Women who are pregnant or lactating History of vesicoureteral reflux or an indwelling urinary stent Participation in any other research protocol involving administration of an investigational agent within 1 month prior to study entry History of radiation to the pelvis History of interstitial lung disease and/or pneumonitis Evidence of metastatic disease
| Event Type | Organ System | Event Term | Phase 1: ABI-009 100 mg/Week | Phase 1: ABI-009 200 mg/Week | Phase 1: ABI-009 100 mg 2×/Week | Phase 1: ABI-009 300 mg/Week | Phase 1: ABI-009 400 mg/Week | Phase 2: ABI-009 400 mg/Week + Gemcitabine 2000 mg/Week |
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The primary endpoint of the Phase 1 study is DLT following intravesical administration of ABI-009 in patients with BCG refractory or recurrent nonmuscle-invasive transitional cell carcinoma (TCC) of the bladder to identify maximum deliverable dose (MDD). Systemic DLT will be defined as any grade systemic toxicity using the NCI CTCAE version 4.0. Local dose limiting toxicity was defined as grade 3 or 4 bladder toxicity (hematuria, dysuria, urinary retention, urinary frequency/urgency, or bladder spasms) using the NCI CTCAE version 4.0.
The primary objective of the Phase 2 study is to evaluate the utility (potential for clinical efficacy) of ABI-009 in combination with gemcitabine in the treatment of BCG refractory or recurrent nonmuscle-invasive TCC of the bladder. Response rate will be measured and documented at the 6-week post-treatment assessment, including cystoscopy with biopsy. A complete response is defined as a cancer-negative biopsy at the 6-week post-treatment cystoscopy. No response will be defined as positive cystoscopic biopsy.
Response rate will be measured and documented at the 6-week post-treatment assessment, including cystoscopy with biopsy. A complete response is defined as a cancer-negative biopsy at the 6-week post-treatment cystoscopy. No response will be defined as positive cystoscopic biopsy.
