Non-muscle Invasive Bladder Cancer (NMIBC)Phase 1/2NCT02009332
Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer
A Phase 1/2 study testing ABI-009 and Gemcitabine in people with Non-muscle Invasive Bladder Cancer (NMIBC), run by Aadi Bioscience, Inc. at 2 sites in United States.
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle Invasive Bladder Cancer (NMIBC)
- What is being tested?
- ABI-009 and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Apr 2014to 1 Dec 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 16Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University Medical Center
New York, New York, 10032
About this study
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
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
- Being tested
- ABI-009, Gemcitabine
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABI-009Drug
Also called nab-sirolimus, nab-rapamycin
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.
GemcitabineDrug
Gemcitabine is administered after ABI-009 in the Phase 2 study.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: ABI-009 100 mg/week | Experimental | 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 Receives: Drug: ABI-009 |
| Phase 1: ABI-009 200 mg/week | Experimental | 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 Receives: Drug: ABI-009 |
| Phase 1: ABI-009 100 mg 2×/week | Experimental | 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 Receives: Drug: ABI-009 |
| Phase 1: ABI-009 300 mg/week | Experimental | 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 Receives: Drug: ABI-009 |
| Phase 1: ABI-009 400 mg/week | Experimental | 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 Receives: Drug: ABI-009 |
| Phase 2: ABI-009 400 mg/week + Gemcitabine 2000 mg/week | Experimental | 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 Receives: Drug: ABI-009; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months)
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.
Measured: End of Study [EOS, 3 months]
Secondary outcomes (1)
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.
Measured: End of Study [EOS, 3 months]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2013 (estimated)
- Study start9 Apr 2014
- Primary completion1 Dec 2019
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-muscle Invasive Bladder Cancer (NMIBC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aadi Bioscience, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- James McKiernan, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02009332
- Sponsor's protocol ID
- BC001
- Other IDs
- 1R42CA171552-01
- Status last verified
- May 2021
- First submitted
- 8 Dec 2013
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02009332
- Acronym / sponsor ID
- BC001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Aadi Bioscience, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 9 Apr 2014 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 12 Dec 2013 (estimated)
- Results
- Posted 8 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase 1: ABI-009 100 mg/week | Experimental | Drug: ABI-009Phase 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: ABI-009 200 mg/week | Experimental | Drug: ABI-009Phase 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: ABI-009 100 mg 2×/week | Experimental | Drug: ABI-009Phase 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: ABI-009 300 mg/week | Experimental | Drug: ABI-009Phase 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: ABI-009 400 mg/week | Experimental | Drug: ABI-009Phase 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 |
| Phase 2: ABI-009 400 mg/week + Gemcitabine 2000 mg/week | Experimental | Drug: ABI-009, Drug: GemcitabineABI-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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).
- 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
- Hepatic inclusion within 2 weeks of entry
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABI-009Also: nab-sirolimus, nab-rapamycinABI-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. | Drug | Phase 1: ABI-009 100 mg 2×/week, Phase 1: ABI-009 100 mg/week, Phase 1: ABI-009 200 mg/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 |
| GemcitabineGemcitabine is administered after ABI-009 in the Phase 2 study. | Drug | Phase 2: ABI-009 400 mg/week + Gemcitabine 2000 mg/week |
Primary outcome
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.
1 secondary outcome
Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009
Time frame: End of Study [EOS, 3 months]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Non-muscle Invasive Bladder Cancer (NMIBC)
RecruitingPhase 1
A Study to Learn About the Study Medicine PF-08052667 in People With Bladder Cancer
Non-muscle Invasive Bladder Cancer
Recruiting
Using Urine Tumor DNA to De-Intensify Surveillance in Non-Muscle Invasive Bladder Cancer
Non-muscle Invasive Bladder Cancer (NMIBC)
Active, not recruitingPhase 3
A Study of TAR-200 Versus Intravesical Chemotherapy in Participants With Recurrent High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC) After Bacillus Calmette-Guérin (BCG)
Non-Muscle Invasive Bladder Neoplasms
RecruitingPhase 2
Disitamab Vedotin Plus Intravesical Mitomycin C in HER2-Expressing Intermediate- to High-Risk Non-Muscle-Invasive Bladder Cancer
Non-Muscle-Invasive Bladder Cancer (NMIBC)
RecruitingPhase 3
A Study to Evaluate TAR-210 Versus Single Agent Intravesical Cancer Treatment in Participants With Bladder Cancer
Non-Muscle Invasive Bladder Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James McKiernan, MD principal investigator
Columbia University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ABI-009 and Gemcitabine in people with Non-muscle Invasive Bladder Cancer (NMIBC), run by Aadi Bioscience, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.