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

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ClinicalTrials.gov Identifier: NCT02009332
Recruitment Status : Completed
First Posted : December 12, 2013
Results First Posted : June 8, 2021
Last Update Posted : June 8, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Aadi, LLC

Tracking Information
First Submitted Date  ICMJE December 8, 2013
First Posted Date  ICMJE December 12, 2013
Results First Submitted Date  ICMJE March 8, 2021
Results First Posted Date  ICMJE June 8, 2021
Last Update Posted Date June 8, 2021
Actual Study Start Date  ICMJE April 9, 2014
Actual Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2021)
  • Phase 1: Dose Limiting Toxicities (DLT) Following Intravesical Administration of ABI-009 [ Time Frame: Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months) ]
    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 [ Time Frame: End of Study [EOS, 3 months] ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2013)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: End of Study [EOS, 3 months] and follow-up [1 year] ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2021)
Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 [ Time Frame: End of Study [EOS, 3 months] ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2013)
Number of Participants achieving a complete response as a Measure of Efficacy [ Time Frame: End of Study [EOS, 3 months] and follow-up [1 year] ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-muscle Invasive Bladder Cancer (NMIBC)
Intervention  ICMJE
  • 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.
    Other Names:
    • nab-sirolimus
    • nab-rapamycin
  • Drug: Gemcitabine
    Gemcitabine is administered after ABI-009 in the Phase 2 study.
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: ABI-009
  • Experimental: 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
    Intervention: Drug: ABI-009
  • Experimental: 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
    Intervention: Drug: ABI-009
  • Experimental: 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
    Intervention: Drug: ABI-009
  • Experimental: 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
    Intervention: Drug: ABI-009
  • Experimental: 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
    Interventions:
    • Drug: ABI-009
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2019)
21
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2013)
40
Actual Study Completion Date  ICMJE December 1, 2019
Actual Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02009332
Other Study ID Numbers  ICMJE BC001
1R42CA171552-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Aadi, LLC
Study Sponsor  ICMJE Aadi, LLC
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: James McKiernan, MD Columbia University
PRS Account Aadi, LLC
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP