A Combined Phase I & II Trial of Intravesicular Abraxane, a Nanoparticle Albumin-bound Paclitaxel, for Treatment-refractory Transitional Cell Carcinoma of the Urinary Bladder
| City: |
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New York |
| State: |
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New York |
| Zip Code: |
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10032 |
| Conditions: |
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Bladder Cancer |
| Purpose: |
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The intravesical treatment of bladder cancer with Abraxane is more desirable than other
taxanes due to its ability to be diluted in water and not lipid-based solutions allowing it
greater access to sites in the bladder. Thus, we are interested in investigating Abraxane's
safety, toxicity, and efficacy profile for the treatment of recurrent transitional cell
cancer of the urinary bladder in a combined phase I & II trial. The phase I trial is
designed as a dose-escalation study with cohorts of threes that will enroll a maximum of 18
patients. Dose increases will occur in groups of three patients, with each successive group
receiving an increased concentration of Abraxane intravesically. No dose increase will
occur until each member of the previous cohort has undergone the first instillation of the
medication without experiencing a dose-limiting toxicity (DLT). Any patient who experiences
a DLT will be removed from the trial and treated appropriately.
If one patient in the cohort experiences a DLT an additional three patients will be enrolled
and treated at that dose-level. If none of the additional three patients experience a DLT,
the next group of patients will be started on the next higher dose level.
If at any dose level, two or more patients experience a DLT the previous dose level will be
considered as the maximum tolerated dose (MTD). An additional three patients (for a total
of six patients) will then be treated at the MTD. If less than two patients experience a
DLT this dose level will be established as the MTD. The phase II aspect is designed in a
Simon II stage format in which to satisfy our study powering, the first stage there will be
10 patients enrolled. If there are 2 or more successful treatments in that group (negative
urine cytology and bladder biopsy after 6 months), then the first stage will pass the
rejection rule, and up to another 19 patients will be enrolled. If at any point in the
study, there have been a total of 6 or more successes, then the phase II aspect will be
considered a successful trial and the study will be completed at that point.
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| Study Summary: |
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| Criteria: |
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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
superficial recurrent bladder cancer refractory to standard intravesical therapy.
This will include stage Ta, T1, Tis and exclude all patients with muscle invasion
(T2). All patients with stage Ta will require documentation of high-grade histology.
All grossly visible disease must be fully resected and pathologic stage will be
confirmed at the institution where the patient is enrolled. Patients must exhibit
disease recurrence after receiving some form of standard intravesical therapy,
including BCG, mitomycin, interferon or any combination thereof.
- Age > 18 and must be able to read, understand and sign informed consent
- Performance Status: ECOG 0,1 (See Appendix II )
- Peripheral neuropathy: must be < grade 1
- 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 ≤ 2.0 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, i.e., IUD, Birth control pills, Depo-Provera, and condoms while on
treatment and for 3 months after their participation in the study ends.
- No intravesical therapy within 6 weeks of study entry
- No prior radiation to the pelvis
Exclusion Criteria:
- Prior systemic docetaxel or paclitaxel therapy.
- Any other malignancy diagnosed within 2 years of study entry (except basal or
squamous cell skin cancers or non-invasive 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 3 months prior to study entry aside from the phase I
segment of this study.
- History of neuropathy of any cause
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| NCT ID: |
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NCT00583349 |
| Primary Contact: |
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Principal Investigator
James M McKiernan, MD
Columbia University Medical Center, Urology
Sam Cammack
Phone: 212-305-1207
Email: ac2239@columbia.edu
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| Backup Contact: |
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N/A |
| Location Contact: |
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New York, New York 10032
United States
LaMont J Barlow
Phone: 212-305-6665
Email: ljb2119@columbia.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 24, 2013 |
| Modifications to this listing: |
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