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

Non-muscle Invasive Bladder Cancer (NMIBC) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02009332
• Other study ID #: BC001
• Secondary ID: 1R42CA171552-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 9, 2014
• Est. completion date: December 1, 2019

Study information

• Verified date: May 2021
• Source: Aadi, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Non-muscle Invasive Bladder Cancer (NMIBC)
• Urinary Bladder Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Aadi, LLC	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Dose Limiting Toxicities (DLT) Following Intravesical Administration of ABI-009	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.	Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months)
Primary	Phase 2: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 and Gemcitabine	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.	End of Study [EOS, 3 months]
Secondary	Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009	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.	End of Study [EOS, 3 months]