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

Primary Purpose

Non-muscle Invasive Bladder Cancer (NMIBC)

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ABI-009

Gemcitabine

About this trial

This is an interventional treatment trial for Non-muscle Invasive Bladder Cancer (NMIBC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).
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
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
1. Absolute neutrophil count >1,500/mm3
2. Hemoglobin >9.0 g/dl
3. Platelet count >100,000/mm3
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
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

Sites / Locations

Columbia University Medical Center
Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

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

Arm Description

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02009332

First Posted

December 8, 2013

Last Updated

May 12, 2021

Sponsor

Aadi Bioscience, Inc.

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02009332

Brief Title

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

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

April 9, 2014 (Actual)

Primary Completion Date

December 1, 2019 (Actual)

Study Completion Date

December 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aadi Bioscience, Inc.

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-muscle Invasive Bladder Cancer (NMIBC)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1: ABI-009 100 mg/week

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 1: ABI-009 200 mg/week

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 1: ABI-009 100 mg 2×/week

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 1: ABI-009 300 mg/week

Arm Type

Experimental

Arm Description

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

Arm Title

Phase 1: ABI-009 400 mg/week

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ABI-009

Other Intervention Name(s)

nab-sirolimus, nab-rapamycin

Intervention Description

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

Intervention Name(s)

Gemcitabine

Intervention Description

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

Primary Outcome Measure Information:

Title

Phase 1: Dose Limiting Toxicities (DLT) Following Intravesical Administration of ABI-009

Description

Time Frame

Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months)

Title

Phase 2: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 and Gemcitabine

Description

Time Frame

End of Study [EOS, 3 months]

Secondary Outcome Measure Information:

Title

Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009

Description

Time Frame

End of Study [EOS, 3 months]

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James McKiernan, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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