Pre-TURBT TC-3 Gel Intravesical Instillation in NMIBC

NCT ID: NCT01803295

Last Updated: 2017-06-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2017-06-30

Brief Summary

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In the proposed study the investigators aim to evaluate the effect of the standard of care dose (40mg) of MMC mixed with TC-3 gel (with sustained release mechanism on the drug) on low risk recurrent NMIBC lesions and to compare our findings to instillation with the standard mode of instillation- 40mg MMC in water in order to examine our hypothesis that MMC mixed with TC-3 gel will have at least non-inferior and even superior results over the standard instillation mode

The investigators believe that this study is of importance of several aspects:

1. It evaluates a new mode of bladder instillation that may bypass the drawbacks of the current instillation mode.
2. If proved effective this mode of treatment might save the need of TURBT performance and serve as a new mode of tumor ablation.
3. Even if proved partially effective this mode of treatment will diminish tumors size or number thus enable a more limited TURBT procedure.
4. This mode of treatment will enable immediate medical attendance to the patient's tumor recurrence without the waiting period (resulting from queues in the medical centers) for TURBT, which might improve the patient's prognostic outcome.
5. If this experimental treatment will prove to have a better ablative effect, this could be translated to a better prophylactic effect of tumor recurrence.

Detailed Description

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Non-muscle-Invasive Bladder cancer is mainly treated by tumor resection (Trans Urethral Resection - TUR), followed by series of intravesical instillations of prophylactic chemotherapeutic drugs as Mitomycin C (MMC) or BCG. This treatment approach is limited due to rapid dilution the chemotheraputic drug by the incoming urine and clearance by urination.

TheraCoat core technology is based on a reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder.

Prior to instillation, the TC-3 hydrogel, in a liquid state, is mixed with MMC.TC-3 mixed with MMC is instilled to the bladder by a catheter. Following gel insertion to the bladder, the gel solidifies and forms a drug reservoir inside the bladder. Upon contact with urine the gel dissolves and is cleared out from the bladder.

Intravesical MMC instillation using TheraCoat gel is expected to increase treatment efficiency due to prolongation of treatment duration and consequently improving bladder exposure to MMC.

Treatment Protocol - Immediately following baseline cystoscopy and tumor diagnosis and patient undergoes 6 weekly instillations followed by 2-4 weeks healing period.

1st Follow-Up Visit (Pre-Scheduled TURBT Visit): The patient will undergo a second Cystoscopy to compare to the Baseline status and after that a follow-up period: 3,6,9,12 months.

Conditions

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Carcinoma of Urinary Bladder, Superficial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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40 mg MMC gel

Device: TC-3 gel mixed with Mitomycin C (MMC) Six weekly intravesical instillations of 60 cc of TC-3 gel mixed with 40 mg MMC will be instilled using catheter.

Other Name: MMC Gel

Group Type EXPERIMENTAL

40 mg MMC gel

Intervention Type DEVICE

A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder.

Standard of care MMC mixed with water

40 mg MMC mixed with 40cc water. Six weekly intravesical instillations of 40 mg of MMC mixed with 40 cc of water will be instilled using catheter

Group Type ACTIVE_COMPARATOR

Standard of care MMC mixed with water

Intervention Type OTHER

Standard of care 40mg MMC mixed with water

80 mg MMC gel

Device: TC-3 gel mixed with Mitomycin C (MMC) Six weekly intravesical instillations of 60 cc of TC-3 gel mixed with 80 mg MMC will be instilled using catheter.

Other Name: MMC Gel

Group Type EXPERIMENTAL

80 mg MMC gel

Intervention Type DEVICE

A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder

Interventions

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40 mg MMC gel

A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder.

Intervention Type DEVICE

Standard of care MMC mixed with water

Standard of care 40mg MMC mixed with water

Intervention Type OTHER

80 mg MMC gel

A reverse thermal biodegradable gel (TC-3) (low viscosity at 5°C gel appearance at body temperature)for drug retention in the urinary bladder

Intervention Type DEVICE

Other Intervention Names

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MMC-Gel MMC-Gel

Eligibility Criteria

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Inclusion Criteria

1. Patient is 21 years of age or older.
2. Patient has signed Informed Consent Form and is willing and able to abide by the protocol.
3. Naïve or recurrent low grade (LG) NMIBC tumor
4. Recurrent patients - Single or multiple tumors
5. Naive patients - 2 tumors or above
6. No prior history of HG and/or T1 in the past 5 years.
7. No prior history of Tis
8. At least one Tumor ≥ 1 mm as evaluated visually by the investigator.
9. Largest tumor diameter ≤ 30 mm as evaluated visually by the investigator
10. Cystoscopic appearance of papillary Low grade tumor
11. No active urinary tract infection as confirmed by urine culture
12. If the patient is a female of childbearing potential , she is using two acceptable \& effective methods of contraception , until 6 months post treatment
13. If the patient is a male he should use a condom during intercourse, for at least 48 hours post each instillation
14. If the patient is a male that has a partner that is a female of childbearing potential, he should be advised to use two acceptable \& effective methods of contraception until 6 months post treatment.

Exclusion Criteria

1. Carcinoma In Situ (CIS).
2. "High Grade" urine cytology which is conclusive for HG.
3. "High Grade" tumor results in cold cup biopsy.
4. Tumor located in prostatic urethra.
5. Previous systemic chemotherapy in the last 2 years or pelvic radiotherapy.
6. Pregnant or breastfeeding patient.
7. Previous treatment with BCG within the last 12 months.
8. The patient did not have at least 3 months cystoscopically confirmed tumor-free interval between the last TURBT to current tumor recurrence.
9. Treatment with full course of intravesical chemotherapy within the 3 last months.
10. The patient has/had any bladder tumor with histology other than TCC.
11. Known contraindication or hypersensitivity to MMC or gel.
12. The patient has a known history of upper urinary tract urothelial carcinoma, or Renal Cell carcinoma or other renal cancer.
13. The patient has a known urinary retention which, according to the investigator's opinion, might lead to avoid patient receiving the treatment.
14. The patient has a bleeding disorder or a screening platelet count \<50X109/L.
15. The patient has screening hemoglobin \<10 mg/dL.
16. The patient has a condition or a concurrent severe and/or uncontrolled medical or psychiatric disease (e.g. uncontrolled diabetes, compensated congestive heart failure (NYHA III and over), myocardial infarction within 6 months of study, unstable or uncontrolled hypertension or an active uncontrolled infection), which could compromise participation, compliance with scheduled visits and/or completion.
17. The patient participated in an investigational interventional study within the past 90 days.
18. The patient has documented sever vesico-ureteral reflux or an indwelling ureteral stent.
19. The patient has the tumor in the bladder diverticulum.
20. The patient participated in a prior TheraCoat's trial with MMC and TC-3
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UroGen Pharma Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fred Witjes, Prof

Role: PRINCIPAL_INVESTIGATOR

Radboud University Nijmegen Medical Centre, Department of Urology Geert Grooteplein South 10 (659), Nijmegen

Stenzl, Prof.

Role: PRINCIPAL_INVESTIGATOR

Tübingen Universitätsklinik für Urologie

Locations

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Carmel Medical Center of Haifa, Department of Urology

Haifa, , Israel

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Wolfson Medical Center of Holon, Department of Urology

Holon, , Israel

Site Status

Meir medical center

Kfar Saba, , Israel

Site Status

Galil Maaravi Medical Center of Nahariya, Department of Urology

Nahariya, , Israel

Site Status

Rabin Medical Center of Petah Tikva, Department of Urology

Petach Tikvah, , Israel

Site Status

Ziv Medical Center

Safed, , Israel

Site Status

Vita Salute University, San Raffaele Hospital of Milan, Department of Urology

Milan, , Italy

Site Status

S. Andrea Hospital of Rome, Department of Urology

Rome, , Italy

Site Status

Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, , Italy

Site Status

Fundacio Puigvert

Barcelona, , Spain

Site Status

Hospital Universitario Infanta Sofìa of Madrid, Department of Urology

Madrid, , Spain

Site Status

Hôpital HUG of Geneva, Department of Urology

Geneva, , Switzerland

Site Status

Countries

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Israel Italy Spain Switzerland

Other Identifiers

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TAS-4M-CS-0002-0

Identifier Type: -

Identifier Source: org_study_id

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