Clinical Trials /

Safety and Tolerability of TAR-200 in Subjects With Muscle-Invasive Bladder Cancer Who Are Unfit for Radical Cystectomy

NCT03404791

Description:

The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are unfit for radical cystectomy (RC) during an 84-day induction period comprised of four consecutive 21-day dosing cycles.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Tolerability of TAR-200 in Subjects With Muscle-Invasive Bladder Cancer Who Are Unfit for Radical Cystectomy
  • Official Title: A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy

Clinical Trial IDs

  • ORG STUDY ID: TAR-200-103
  • NCT ID: NCT03404791

Conditions

  • Bladder Cancer TNM Staging Primary Tumor (T) T2A
  • Bladder Cancer TNM Staging Primary Tumor (T) T2B
  • Bladder Cancer TNM Staging Primary Tumor (T) T3A
  • Bladder Cancer TNM Staging Primary Tumor (T) T3B

Interventions

DrugSynonymsArms
Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200Radical Cystectomy Ineligible

Purpose

The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are unfit for radical cystectomy (RC) during an 84-day induction period comprised of four consecutive 21-day dosing cycles.

Trial Arms

NameTypeDescriptionInterventions
Radical Cystectomy IneligibleExperimentalTAR-200 is placed into the bladder through an Inserter and gradually releases gemcitabine during the 21-day indwelling period before being removed. Subjects will undergo an 84-day induction period comprised of four consecutive 21-day dosing cycles. Subjects may undergo up to 3 additional dosing cycles as maintenance.
  • Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

Eligibility Criteria

        Inclusion Criteria:

          1. Histological proof of non-metastatic muscle-invasive urothelial cell carcinoma of the
             bladder.

          2. Subject must have been as fully resected as possible per the physician's judgment.

          3. Subjects must be deemed unfit for RC due to comorbid conditions with a risk of
             mortality.

          4. Subjects must refuse or be deemed ineligible for cisplatin-based chemotherapy.

          5. Subject must refuse or not be eligible for radiotherapy.

          6. Life expectancy of at least 4 months.

          7. Adequate bone marrow, liver, and renal function.

          8. Subjects must be willing to undergo a cystoscopy.

          9. Subjects must be willing to undergo a biopsy for assessment of clinical response.

         10. Written informed consent and authorization for release of personal health information
             obtained according to local laws.

         11. Age ≥18 years at the time of informed consent.

         12. Females of childbearing potential must be willing to use an effective method of
             contraception (hormonal or barrier method of birth control; abstinence) from the time
             consent is signed until 4 weeks after treatment discontinuation. Subject's partner
             must also use barrier protection while subject is on study until 4 weeks after
             treatment discontinuation.

         13. Males must be willing to use an effective method of contraception/method to avoid
             seminal transfer (barrier method or abstinence) from the time consent is signed until
             4 weeks after treatment discontinuation. Subject's partner must also use barrier
             protection while subject is on study until 4 weeks after treatment discontinuation.

         14. Females of childbearing potential must have a negative pregnancy test within 21 days
             prior to Study Day 0.

        Exclusion Criteria:

          1. Other active malignancies.

          2. Presence of any bladder or urethral anatomic feature that in the opinion of the
             Investigator may prevent the safe placement, indwelling use, or removal of TAR-200.

          3. Pyeloureteral tube externalized to the skin (ureteral stent or unilateral nephrostomy
             tube is allowed).

          4. Evidence of bladder perforation during diagnostic cystoscopy.

          5. Bladder post-void residual volume (PVR) of >750 mL.

          6. Concurrent clinically significant infections as determined by the treating
             Investigator.

          7. Known hypersensitivity to gemcitabine (or other drug excipients) or chemically related
             drugs.

          8. Known hypersensitivity to the device constituent or TARIS Inserter materials.

          9. Use of an investigational product within 30 days or 5 half-lives, whichever is longer,
             preceding Study Day 0.

         10. Female subject who is lactating/breastfeeding.

         11. Difficulty providing blood samples.

         12. Unwilling or unable to provide informed consent or comply with the requirements of
             this protocol, including the presence of any condition (physical, mental or social)
             that is likely to affect the subject's return for scheduled visits and follow-up.

         13. Other unspecified reasons that, in the opinion of the Investigator, make the subject
             unsuitable for enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 as assessed by CTCAE V4.0
Time Frame:Study Day 0 to Study Day 84
Safety Issue:
Description:Will be assessed through the duration of the study by reported AEs

Secondary Outcome Measures

Measure:Proportion of subjects with clinical complete response (cCR)
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Will be assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated)
Measure:Proportion of subjects with clinical partial response (cPR)
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Will be assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated)
Measure:Proportion of subjects with stable disease (SD)
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Will be assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated)
Measure:Proportion of subjects with progression
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Will be assessed by cystoscopy, pelvic computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and biopsy (at 12 weeks only, unless clinically indicated)
Measure:Symptom control
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Defined as changes in bladder-related symptoms per the protocol-specified bladder symptom and toxicity grading system
Measure:Time to intervention for symptom control
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Defined as the time from date of the first TAR-200 insertion to the date of intervention for symptom palliation
Measure:Time to progression
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Defined as the time from the date of the first TAR-200 insertion to the date of first occurrence of progression
Measure:Proportion of subjects undergoing post-treatment interventions by 3, 6, 9, and 12 months
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Number of subjects undergoing post-treatment interventions compared to all subjects
Measure:Proportion of subjects surviving at 12 months
Time Frame:Approximately Study Day 0 to Study Day 360
Safety Issue:
Description:Number of subject surviving at 12 months compared to all subjects

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Taris Biomedical LLC

Trial Keywords

  • Bladder Cancer
  • Urothelial Carcinoma
  • Cystectomy
  • Radical Cystectomy

Last Updated

April 4, 2018