Pre-TURBT TC-3 Gel Intravesical Instillation in NMIBC

NCT01803295 | Completed

• 1 other identifier: TAS-4M-CS-0002-0
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 13

Brief Summary

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. 1.It evaluates a new mode of bladder instillation that may bypass the drawbacks of the current instillation mode.
2. 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. 3.Even if proved partially effective this mode of treatment will diminish tumors size or number thus enable a more limited TURBT procedure.
4. 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. 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.

Conditions

Carcinoma of Urinary Bladder, Superficial

Keywords

Non Muscle Invasive Bladder Cancer; Intravesical instillation; Mitomycin C; Hydrogel Reverse thermal gelation; Drug retention; Urinary Bladder Neoplasms; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Mitomycin

Outcome Measures

Primary Outcomes (2)

• ablative effect of pre-TURBT intravesical instillations of the treatments on The bladder lesion(s) of NMIBC patients

  Cystoscopic and pathological effect (evaluated during TUR-BT visit) of pre-TURBT intravesical instillations with 40 mg of MMC mixed with 60cc TC-3 Hydrogel on bladder lesion(s) of NMIBC patients. At To, which is the time of identification of a recurrent tumor by cystoscopy, the number, size and location of the lesions will be documented and photographed. Each tumor size will be evaluated by photographing a ureter catheter adjacent to the tumor. Since the ureter catheter diameter is a pre-known variable, the tumor diameter can be calculated using specific software developed for study purposes. Photography of the tumor with a pre-known diameter ureter catheter will be performed during the same cystoscopy as described above and will be evaluated by a central clinic for uniformity of measurements, and the results of these measurements will serve for the post study evaluation of the change in tumor diameter

  2 years

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability rate.

  Demonstration of Pre-TURBT TC-3 gel-MMC instillation safety and adverse event rate.Adverse events will be defined as any adverse change in health or side effect that occurs in the clinical trial participant while the patient is receiving the treatment or until the completion of the post-treatment follow-up cystoscopy.

  2 years

Other Outcomes (3)

• Comparison of the cystoscopic and pathological effect between the 2 groups.

  2 years

• • Comparison of one year tumor recurrence rate between both treatment groups

  2 years

• • Demonstration that blood levels of MMC following Pre-TURBT TC-3 gel-MMC instillation are below the toxic level (400ng/ml) known in the art for IV MMC administration

  1 year

Study Arms (3)

40 mg MMC gel

EXPERIMENTAL

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

Device: 40 mg MMC gel

Standard of care MMC mixed with water

ACTIVE COMPARATOR

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

Other: Standard of care MMC mixed with water

80 mg MMC gel

EXPERIMENTAL

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

Device: 80 mg MMC gel

Interventions

40 mg MMC gel 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.

Also known as: MMC-Gel

40 mg MMC gel

Standard of care MMC mixed with water OTHER

Standard of care 40mg MMC mixed with water

Standard of care MMC mixed with water

80 mg MMC gel 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

Also known as: MMC-Gel

80 mg MMC gel

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Carcinoma In Situ (CIS).
• "High Grade" urine cytology which is conclusive for HG.
• "High Grade" tumor results in cold cup biopsy.
• Tumor located in prostatic urethra.
• Previous systemic chemotherapy in the last 2 years or pelvic radiotherapy.
• Pregnant or breastfeeding patient.
• Previous treatment with BCG within the last 12 months.
• The patient did not have at least 3 months cystoscopically confirmed tumor-free interval between the last TURBT to current tumor recurrence.
• Treatment with full course of intravesical chemotherapy within the 3 last months.
• The patient has/had any bladder tumor with histology other than TCC.
• Known contraindication or hypersensitivity to MMC or gel.
• The patient has a known history of upper urinary tract urothelial carcinoma, or Renal Cell carcinoma or other renal cancer.
• The patient has a known urinary retention which, according to the investigator's opinion, might lead to avoid patient receiving the treatment.
• The patient has a bleeding disorder or a screening platelet count \<50X109/L.
• The patient has screening hemoglobin \<10 mg/dL.

Sponsors & Collaborators

• UroGen Pharma Ltd.: lead

Study Sites (13)

Carmel Medical Center of Haifa, Department of Urology

Haifa, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

Wolfson Medical Center of Holon, Department of Urology

Holon, Israel

Location

Meir medical center

Kfar Saba, Israel

Location

Galil Maaravi Medical Center of Nahariya, Department of Urology

Nahariya, Israel

Location

Rabin Medical Center of Petah Tikva, Department of Urology

Petach Tikvah, Israel

Location

Ziv Medical Center

Safed, Israel

Location

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

Milan, Italy

Location

S. Andrea Hospital of Rome, Department of Urology

Rome, Italy

Location

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

Salerno, Italy

Location

Fundacio Puigvert

Barcelona, Spain

Location

Hospital Universitario Infanta Sofìa of Madrid, Department of Urology

Madrid, Spain

Location

Hôpital HUG of Geneva, Department of Urology

Geneva, Switzerland

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases

Interventions

Water

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Fred Witjes, Prof

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

  PRINCIPAL INVESTIGATOR

• Stenzl, Prof.

  Tübingen Universitätsklinik für Urologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: March 4, 2013
• Study Start: June 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: June 1, 2017
• Last Updated: June 16, 2017

Record last verified: 2017-06

Locations

CH (1); ES (2); IT (3); IL (7)