Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urologic Neoplasms

Urologic Diseases

Urinary Bladder Diseases

Urogenital Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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).

Administered via intravesical instillation.

TSD-001

Michael Oefelein, MD

This is a single-arm, phase 1/2a study of formulated paclitaxel in subjects with low-grade, noninvasive papillary carcinoma (stage Ta) of the bladder.

Part 1 of the study will enroll 6 subjects (3 per cohort) with low-grade, stage Ta transitional cell carcinoma (TCC) of the bladder who will receive escalating doses of paclitaxel formulated as TSD-001 every 2 weeks for 6 treatments until Dose Limiting Toxicity (or until the Maximum Deliverable Dose) is observed (Maximum Tolerated Dose established).

Part 2 of the study will enroll an additional 10 subjects with low-grade, stage Ta (uni-or multifocal) TCC of the bladder who will receive weekly TSD-001 for 6 weeks at the highest nontoxic dose (i.e., MTD) established in part 1 of the study. May meet definition of low grade without histological tissue diagnosis if on cystoscopic assessment they have a solitary papillary tumor.

Part 3 of the study will continue to track subjects enrolled in Parts 1 and 2 to determine rates of disease-free survival.

Proliposomal Intravesical Paclitaxel for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer

A Phase 1/2a Pilot Study of Intravesical TSD-001 for Treatment of Low-Grade, Stage Ta, Non Muscle Invasive Bladder Cancer

Long term follow-up (2 years post initial treatment) to determine when histological tissue diagnosis evidence of recurrence occurs for subjects exposed to TSD-001 in part 1 or part 2. Cystoscopic surveillance will be performed as standard of care approximately every 3 months from last endoscopic assessment in part 1 or part 2 until 24 months (from initial instillation).

Dose immediately preceding the dose at which DLT occurs or when a MDD is reached.

Determine the marker lesion response rate using the MTD established in part 1.

Determine the local (bladder urine) and systemic (peripheral blood) paclitaxel concentrations before and after intravesical exposure to TSD-001 at all doses. Blood and urine samples will be collected 15 (± 15) minutes before and 2 hours (± 10 minutes) after each instillation.

Determine the local (bladder urine) paclitaxel concentrations 15 (± 15) minutes before, and 2 hours (± 10 minutes) after the third intravesical instillation of TSD-001.

Determine the systemic (peripheral blood) paclitaxel concentration 2 hours (± 10 minutes) after the first intravesical instillation of TSD-001. Determine the systemic (peripheral blood) paclitaxel concentrations 15 (± 15) minutes before, and 2 hours (± 10 minutes) after the third intravesical instillation of TSD-001.

Characterize the severity and frequency of AEs following intravesical administration of TSD-001.

Spots Global Cancer Trial Database for bladder cancer cell transitional