Bladder Cancer, Bladder Cancer Cell Transitional, Non-Muscle Invasive Bladder Cancer, Transitional Cell Carcinoma of the Bladder, Urinary Bladder, Urinary Bladder Diseases, Urinary Bladder Neoplasms, Urogenital Neoplasms, Urologic Diseases, Urologic Neoplasms
Conditions
Keywords
NMIBC, Paclitaxel, Antineoplastic Agents, Bladder Cancer
Brief summary
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.
Interventions
DRUGTSD-001
Administered via intravesical instillation.
Sponsors
TesoRx Pharma, LLC
Lipac Oncology LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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%).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum Tolerated Dose or Maximum Deliverable Dose (MDD) | 12 weeks | Dose immediately preceding the dose at which DLT occurs or when a MDD is reached. |
| Part 2: Marker Lesion Response Rate | 12 weeks (Cohort 1) or 15 weeks (Cohort 2) | Determine the marker lesion response rate at final assessment visit for subjects that received the MDD established in part 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Determine Paclitaxel Concentrations | 10 weeks | 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 were collected 15 (± 15) minutes before and 2 hours (± 10 minutes) after each instillation. Results are presented for different dose levels administered during dose escalation. The remaining results are grouped by cohort. |
| Part 2: Determine Paclitaxel Concentrations | Week 2 (pre and post dose) | Determine the systemic (peripheral blood) paclitaxel concentrations 15 (± 15) minutes before, and 2 hours (± 10 minutes) after the third intravesical instillation (Week 2) of TSD-001. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | 2 years | Long-term follow-up to determine when histological tissue diagnosis evidence of recurrence occurs for subjects after complete TURBT and exposure to TSD-001 in part 1. Cystoscopic surveillance was performed every 3 months from the last endoscopic assessment in part 1 until 24 months (from initial TURBT and instillation). Part 2 subjects, different than part 1 subjects, were followed for marker lesion response and did not have standardized TURBT timing to use as a baseline and so are not included in these reported RFS rates. Recurrence-free survival is no histological evidence of transitional cell carcinoma (TCC) recurrence in the time outlined for the TCC risk level. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TSD-001 Administration Part 1, Cohort 1 Part 1, Cohort 1: For the first 3 subjects enrolled, the initial dose was 10 mg in Sterile Water for Injection (SWFI). TSD-001 was planned to be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on the subject's tolerability of the procedure). As Dose Limiting Toxicity(DLT) did not develop, intravesical instillation 14 days later was titrated up according to the schedule (25, 50, 75, 100, 150 mg in SWFI).
TSD-001: Administered via intravesical instillation. | 3 |
| TSD-001 Administration Part 1, Cohort 2 Part 1, Cohort 2: For the next 3 subjects enrolled, the initial dose was 90 mg in SWFI. TSD-001 was planned to be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on the subject's tolerability of the procedure). As DLT did not develop, intravesical instillation 14 days later was titrated up according to the schedule (180, 270, 360, 450, and 540 mg in SWFI).
As no DLT was observed in the first 6 subjects (cohorts 1 and 2) after titration up, the maximum deliverable dose (MDD) was defined as 360 mg and the dose was recommended for part 2 of the study.
TSD-001: Administered via intravesical instillation. | 3 |
| TSD-001 Administration Part 2, Cohort 1 In part 2, cohort 1, the MDD of 360 mg, established in part 1, was provided weekly via the intravesical route.
During part 2, cohort 1, 6 additional subjects received intravesical instillations of TSD-001 via urethral catheterization of the urinary bladder at the MDD established in part 1 at weekly intervals for 6 consecutive weeks. TSD-001 was planned to be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on the subject's tolerability of the procedure).
TSD-001: Administered via intravesical instillation. | 6 |
| TSD Administration Part 2, Cohort 2 In part 2, cohort 1, the MDD of 360 mg, established in part 1, was provided weekly via the intravesical route.
During part 2, cohort 2, 3 additional subjects received intravesical instillations of TSD-001 via urethral catheterization of the urinary bladder at the MDD established in part 1 at weekly intervals for 8 consecutive weeks. TSD-001 was planned to be retained in the bladder for 2 hours (1 hour or more will be acceptable, depending on the subject's tolerability of the procedure).
TSD-001: Administered via intravesical instillation. | 3 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Sponsor Discontinuation - IP issue for investigation (Bacterial Endotoxin level) | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | TSD-001 Administration Part 1, Cohort 1 | TSD-001 Administration Part 1, Cohort 2 | TSD-001 Administration Part 2, Cohort 1 | TSD Administration Part 2, Cohort 2 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 75.33 years STANDARD_DEVIATION 8.96 | 71.67 years STANDARD_DEVIATION 5.51 | 57.50 years STANDARD_DEVIATION 16.99 | 64.33 years STANDARD_DEVIATION 17.79 | 65.27 years STANDARD_DEVIATION 14.85 |
| European Association of Urology (EAU) Risk Stratification Intermediate Risk | 1 Participants | 3 Participants | 6 Participants | 3 Participants | 13 Participants |
| European Association of Urology (EAU) Risk Stratification Low Risk | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Non-Muscle Invasive Bladder Cancer Recurrent No | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Non-Muscle Invasive Bladder Cancer Recurrent Yes | 1 Participants | 2 Participants | 6 Participants | 3 Participants | 12 Participants |
| Number of Tumor Locations Multifocal | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 10 Participants |
| Number of Tumor Locations Solitary | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 5 Participants |
| Previous Intravesical Therapy No | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 9 Participants |
| Previous Intravesical Therapy Yes | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian/ Not Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White/ Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White/ Not Hispanic or Latino | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 12 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants | 3 participants | 15 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 10 |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 6 / 6 | 2 / 3 | 1 / 10 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 6 | 1 / 3 | 1 / 10 |
Outcome results
Primary
Part 1: Maximum Tolerated Dose or Maximum Deliverable Dose (MDD)
Dose immediately preceding the dose at which DLT occurs or when a MDD is reached.
Time frame: 12 weeks
Population: MITT/PK Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TSD-001 Administration Part 1, Cohort 1 | Part 1: Maximum Tolerated Dose or Maximum Deliverable Dose (MDD) | NA mg |
| TSD-001 Administration Part 1, Cohort 2 | Part 1: Maximum Tolerated Dose or Maximum Deliverable Dose (MDD) | 360 mg |
Primary
Part 2: Marker Lesion Response Rate
Determine the marker lesion response rate at final assessment visit for subjects that received the MDD established in part 1.
Time frame: 12 weeks (Cohort 1) or 15 weeks (Cohort 2)
Population: Per Protocol (PP) Population: The PP population will include subjects in the MITT population who have no major protocol violations.~Note: Modified Intent-to-Treat (MITT) population includes all enrolled subjects who received at least one dose of study drug and have at least one post-baseline measurement of paclitaxel concentration.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TSD-001 Administration Part 1, Cohort 1 | Part 2: Marker Lesion Response Rate | Partial Response | 3 Participants |
| TSD-001 Administration Part 1, Cohort 1 | Part 2: Marker Lesion Response Rate | Complete Response | 0 Participants |
| TSD-001 Administration Part 1, Cohort 1 | Part 2: Marker Lesion Response Rate | Marker Lesion Response | 3 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 2: Marker Lesion Response Rate | Complete Response | 1 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 2: Marker Lesion Response Rate | Partial Response | 1 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 2: Marker Lesion Response Rate | Marker Lesion Response | 2 Participants |
Secondary
Part 1: Determine Paclitaxel Concentrations
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 were collected 15 (± 15) minutes before and 2 hours (± 10 minutes) after each instillation. Results are presented for different dose levels administered during dose escalation. The remaining results are grouped by cohort.
Time frame: 10 weeks
Population: Per Protocol (PP) Population: The PP population will include subjects in the MITT population who have no major protocol violations.~Note: Modified Intent-to-Treat (MITT) population includes all enrolled subjects who received at least one dose of study drug and have at least one post-baseline measurement of paclitaxel concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TSD-001 Administration Part 1, Cohort 1 | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1 | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 19367 ug/L | Standard Deviation 4341 |
| TSD-001 Administration Part 1, Cohort 1 | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1 | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2 | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 72933 ug/L | Standard Deviation 50497 |
| TSD-001 Administration Part 1, Cohort 2 | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2 | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2 | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 4: 50 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 4: 50 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 189667 ug/L | Standard Deviation 73433 |
| TSD-001 Administration Part 1, Cohort 1: Week 4: 50 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 4: 50 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 6: 75 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 6: 75 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 6: 75 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 287333 ug/L | Standard Deviation 134016 |
| TSD-001 Administration Part 1, Cohort 1: Week 6: 75 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 8: 100 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 436000 ug/L | — |
| TSD-001 Administration Part 1, Cohort 1: Week 8: 100 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | — |
| TSD-001 Administration Part 1, Cohort 1: Week 8: 100 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | — |
| TSD-001 Administration Part 1, Cohort 1: Week 8: 100 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1: Week 10: 150 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | — |
| TSD-001 Administration Part 1, Cohort 1: Week 10: 150 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 446000 ug/L | — |
| TSD-001 Administration Part 1, Cohort 1: Week 10: 150 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | — |
| TSD-001 Administration Part 1, Cohort 1: Week 10: 150 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | — |
| TSD-001 Administration Part 1, Cohort 2: Day 1: 90 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Day 1: 90 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Day 1: 90 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 241000 ug/L | Standard Deviation 35539 |
| TSD-001 Administration Part 1, Cohort 2: Day 1: 90 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 2: 180 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 699000 ug/L | Standard Deviation 272567 |
| TSD-001 Administration Part 1, Cohort 2: Week 2: 180 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | .8 ug/L | Standard Deviation 1.4 |
| TSD-001 Administration Part 1, Cohort 2: Week 2: 180 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 2: 180 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 4: 270 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 4: 270 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 4: 270 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 686667 ug/L | Standard Deviation 167861 |
| TSD-001 Administration Part 1, Cohort 2: Week 4: 270 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 6: 360 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 6: 360 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 6: 360 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 1161667 ug/L | Standard Deviation 760795 |
| TSD-001 Administration Part 1, Cohort 2: Week 6: 360 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 8: 450 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 1800000 ug/L | Standard Deviation 606300 |
| TSD-001 Administration Part 1, Cohort 2: Week 8: 450 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 8: 450 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 8: 450 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 10: 540 mg | Part 1: Determine Paclitaxel Concentrations | Predose Urine - Paclitaxel Concentration in Urine collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 10: 540 mg | Part 1: Determine Paclitaxel Concentrations | Predose Plasma - Paclitaxel Concentration in Plasma collected 15 minutes before | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2: Week 10: 540 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Urine - Paclitaxel Concentration in Urine collected 2 hrs post | 1886333 ug/L | Standard Deviation 1317354 |
| TSD-001 Administration Part 1, Cohort 2: Week 10: 540 mg | Part 1: Determine Paclitaxel Concentrations | Postdose Plasma - Paclitaxel Concentration in Plasma collected 2 hrs post | 0 ug/L | Standard Deviation 0 |
Secondary
Part 2: Determine Paclitaxel Concentrations
Determine the systemic (peripheral blood) paclitaxel concentrations 15 (± 15) minutes before, and 2 hours (± 10 minutes) after the third intravesical instillation (Week 2) of TSD-001.
Time frame: Week 2 (pre and post dose)
Population: Per Protocol (PP): This population will include subjects in the MITT population who have no major protocol violations.~Note: The Modified Intent to Treat (MITT) population includes enrolled subjects who received at least one dose of study drug and have at least one post-baseline measurement of paclitaxel concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TSD-001 Administration Part 1, Cohort 1 | Part 2: Determine Paclitaxel Concentrations | Predose | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 1 | Part 2: Determine Paclitaxel Concentrations | Postdose | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2 | Part 2: Determine Paclitaxel Concentrations | Predose | 0 ug/L | Standard Deviation 0 |
| TSD-001 Administration Part 1, Cohort 2 | Part 2: Determine Paclitaxel Concentrations | Postdose | 0 ug/L | Standard Deviation 0 |
Other Pre-specified
Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months
Long-term follow-up to determine when histological tissue diagnosis evidence of recurrence occurs for subjects after complete TURBT and exposure to TSD-001 in part 1. Cystoscopic surveillance was performed every 3 months from the last endoscopic assessment in part 1 until 24 months (from initial TURBT and instillation). Part 2 subjects, different than part 1 subjects, were followed for marker lesion response and did not have standardized TURBT timing to use as a baseline and so are not included in these reported RFS rates. Recurrence-free survival is no histological evidence of transitional cell carcinoma (TCC) recurrence in the time outlined for the TCC risk level.
Time frame: 2 years
Population: The MITT population will include all enrolled subjects who received at least one dose of study drug and had at least one post-baseline measurement of paclitaxel concentration.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TSD-001 Administration Part 1, Cohort 1 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | One Year | Disease-Free | 3 Participants |
| TSD-001 Administration Part 1, Cohort 1 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | One Year | Recurrence Occurred | 0 Participants |
| TSD-001 Administration Part 1, Cohort 1 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | Two Year | Disease-Free | 3 Participants |
| TSD-001 Administration Part 1, Cohort 1 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | Two Year | Recurrence Occurred | 0 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | Two Year | Recurrence Occurred | 1 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | One Year | Disease-Free | 2 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | Two Year | Disease-Free | 2 Participants |
| TSD-001 Administration Part 1, Cohort 2 | Part 3: Rates of Recurrence/Disease-Free Survival in Part 1 Subjects Only at 12 and 24 Months | One Year | Recurrence Occurred | 1 Participants |