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

NCT ID: NCT02009332

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-09
• Study Completion Date: 2019-12-01

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

Conditions

Non-muscle Invasive Bladder Cancer (NMIBC)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: ABI-009 100 mg/week

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

Group Type: EXPERIMENTAL

ABI-009

Intervention Type: DRUG

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.

Phase 1: ABI-009 200 mg/week

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

Group Type: EXPERIMENTAL

ABI-009

Intervention Type: DRUG

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.

Phase 1: ABI-009 100 mg 2×/week

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

Group Type: EXPERIMENTAL

ABI-009

Intervention Type: DRUG

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.

Phase 1: ABI-009 300 mg/week

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

Group Type: EXPERIMENTAL

ABI-009

Intervention Type: DRUG

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.

Phase 1: ABI-009 400 mg/week

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

Group Type: EXPERIMENTAL

ABI-009

Intervention Type: DRUG

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.

Phase 2: ABI-009 400 mg/week + Gemcitabine 2000 mg/week

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

Group Type: EXPERIMENTAL

ABI-009

Intervention Type: DRUG

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

Intervention Type: DRUG

Gemcitabine is administered after ABI-009 in the Phase 2 study.

Interventions

ABI-009

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.

Intervention Type: DRUG

Gemcitabine

Gemcitabine is administered after ABI-009 in the Phase 2 study.

Intervention Type: DRUG

Other Intervention Names

nab-sirolimus; nab-rapamycin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Aadi Bioscience, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James McKiernan, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R42CA171552-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BC001

Identifier Type: -

Identifier Source: org_study_id