Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer
Bladder Cancer Cell Transitional, Non-Muscle Invasive Bladder Cancer, Bladder Cancer
About this trial
This is an interventional treatment trial for Bladder Cancer Cell Transitional focused on measuring NMIBC, Paclitaxel, Antineoplastic Agents
Eligibility Criteria
Inclusion Criteria:
- Has a diagnosis of low grade (G1 or G2), uni- or multifocal papillary appearing bladder tumor, stage Ta.
- For part 1, subject will have ≥ 1 and ≤ 5 tumors (prior to TURBT), none of which exceeds 3.0 cm in diameter; for part 2, patient will have ≥ 2 and ≤ 5 tumors (prior to TURBT), none of which exceeds 3.0 cm in diameter (resection loop ~1 cm), OR, for part 2, subject meets this inclusion if on cystoscopic assessment they have a solitary papillary tumor (> 0.5 cm and ≤ 2.0 cm in diameter)..
- Subject is surgical candidate for TURBT as part of normal NMIBC treatment plan. For part 1, successful completion of TURBT procedure. For part 2, successful completion of cystoscopic assessment/TURBT procedure with one marker lesion left intact; the marker lesion should be > 0.5 cm and < 2.0 cm in diameter.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Peripheral neuropathy grade 1 or less.
- Adequate hematological, hepatic, and renal parameters; i.e., hemoglobin > 10 g/dL, creatinine < 3.5 mg/dL, bilirubin < 1.5 mg/dL , and aspartate aminotransferase, alanine aminotransferase < 50 U/L, and alkaline phosphatase < 130 U/L.
- All sexually active subjects of reproductive potential are required to use or start using a reliable method of birth control at least 2 weeks prior to study enrollment, throughout the study, and for at least 3 months following completion of study therapy.
- Females of childbearing potential must have a negative pregnancy test within 30 days prior to enrollment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test.
- For male subjects, the digital rectal examination must not be suspicious for carcinoma of the prostate.
- Able to retain bladder instillations for up to 120 minutes (± 15 minutes).
Exclusion Criteria:
- Has an active concurrent malignancy/life-threatening disease. If there is a history of prior malignancies/life-threatening diseases, the subject is to be disease free for at least 5 years. Subjects with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. Subjects will not be excluded for recurrent NMIBC, basal or squamous cell skin cancers, or noninvasive cancer of the cervix.
- Has positive urine cytology for urothelial malignancy at screening.
- Has an active uncontrolled infection, including a urinary tract infection, underlying medical condition, or other serious illness that would impair the ability of the subject to receive protocol treatment.
- Previous intravesical therapy within 6 months of study entry.
- Prior radiation to the pelvis.
- Participated in a previous clinical trial or used any investigational drugs, biologics, or devices within 90 days prior to study treatment or plans to use any of these during the course of the study.
- Has had any previous exposure to paclitaxel or docetaxel in the last 5 years.
- Has or has ever had: upper tract TCC; urethral tumor (prostatic urethra included); any invasive bladder tumor known to be other than tumor Ta, low-grade (G1-G2); any evidence of lymph node or distant metastasis; any bladder tumor with histology other than TCC; or carcinoma in situ (CIS).
- Has a tumor in a bladder diverticulum
- Concurrent treatment with any chemotherapeutic agent.
- History of vesicoureteral reflux.
- An indwelling ureteral stent.
- Has received any pelvic radiotherapy (including external beam and/or brachytherapy.)
- Has a bleeding disorder or a screening platelet count < 100×109/L.
- Has an active diagnosis of interstitial cystitis.
- For subjects with recurrent tumor, the subject had at least a 6-month cystoscopically confirmed tumor-free interval between the last tumor recurrence and screening cystoscopic examination.
- Presence of poorly controlled diabetes mellitus (glycated hemoglobin [HgbA1c] > 9.0%).
Sites / Locations
- Urological Associates of Southern Arizona, PC
- Trovare Clinical Research
- Tower Urology
- Chesapeake Urology Associates
- Carolina Urologic Research Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
TSD-001 Administration Part 1, Cohort 1
TSD-001 Administration Part 1, Cohort 2
TSD-001 Administration Part 2
Part 1, Cohort 1: For the first 3 subjects enrolled, the initial dose will be 10 mg in Sterile Water for Injection (SWFI). TSD-001 will be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on subject's tolerability of the procedure). If Dose Limiting Toxicity(DLT) does not develop, intravesical instillation 14 days later will be titrated up according to the schedule (25, 50, 75, 100, 150 mg in SWFI) until DLT (defined as any grade 3 or 4 toxicity or prolonged [greater than 14 days] grade 2 toxicity) is observed.
Part 1, Cohort 1: For the next 3 subjects enrolled, the initial dose will be 90 mg in SWFI. TSD-001 will be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on subject's tolerability of the procedure). If DLT does not develop, intravesical instillation 14 days later will be titrated up according to the schedule (180, 270, 360, 450, and 540 mg in SWFI) until DLT (defined as any grade 3 or 4 toxicity or prolonged [greater than 14 days] grade 2 toxicity) is observed. If no DLT is observed in the first 6 subjects (cohorts 1 and 2) after titration up to 540 mg, then the maximum deliverable dose (MDD) will be defined and dose recommended for part 2 of the study.
In part 2, the dose will be selected as the MTD/MDD, established in part 1 and provided weekly via the intravesical route. During part 2, up to 10 additional subjects will receive intravesical instillations of TSD-001 via urethral catheterization of the urinary bladder at the MTD/MDD established in part 1 at weekly intervals for 6 consecutive weeks. TSD-001 will be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on subject's tolerability of the procedure).