Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

NCT03335059 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: RITE-1
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

This study will determine whether Synergo® RITE + MMC treatment is efficacious as second-line therapy for CIS NMIBC BCG-unresponsive patients with or without papillary NMIBC, through examination of the complete response rate (CRR) and disease-free duration for complete responders. The study will also explore progression-free survival time, bladder preservation rate, and overall survival time. The study will address an unmet need to identify a treatment effective in both ablating the disease and providing a prolonged disease-free period for patients. Ideally, the treatment will delay progression to invasive disease, thus preserving the bladder.

Conditions

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

Keywords

BCG; Bacillus Calmette-Guérin; CIS; BCG-unresponsive; Synergo; chemohyperthermia; thermochemotherapy; RF; radio frequency; RITE

Outcome Measures

Primary Outcomes (1)

• complete response rate (CRR)

  * no CIS * no papillary HG tumor * no papillary T1 tumor * no extra-vesical UC tumor * no progression a patient will be considered a complete responder only if all the criteria above are met. Patients experiencing a new occurrence of a benign tumor or low-grade Ta will be allowed to continue in the study (tumor will be resected); such an occurrence will not constitute an event in the primary analysis. Patients with tumors of the ostium and/or upper tract and/or prostatic urethra will be considered to have achieved a complete response in the primary analysis but will be removed from the study.

  3 months after the initiation of study therapy

Secondary Outcomes (1)

• disease-free duration of complete response (DCR)

  through study completion, up to 33 months

Study Arms (1)

Synergo® RITE + MMC

EXPERIMENTAL

Bladder radiofrequency-induced hyperthermia will be delivered in combination with each instillation of MMC in accordance with the Sponsor operational guidelines.

Combination Product: Synergo® RITE + MMC

Interventions

Synergo® RITE + MMC COMBINATION_PRODUCT

Subjects will receive a series of induction followed by a series of maintenance bladder instillations of Synergo® RITE + MMC

Also known as: radiofrequency hyperthermia with mitomycin C, RF hyperthermia with mitomycin C, thermochemotherapy, chemohyperthermia, CHT, radio-frequency hyperthermia with mitomycin C

Synergo® RITE + MMC

Eligibility Criteria

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

You may qualify if:

• Patients with current CIS of the bladder, with or without coexisting papillary Ta/T1 NMIBC tumor(s), who experienced an occurrence or recurrence of CIS within 12 months of completion of adequate BCG7 therapy. An adequate BCG regimen shall consist of at least 2 courses of BCG where the first course (induction) must have included at least 5 of 6 weekly treatments and the second course may have included a re-induction (at least 2 of 6 treatments) or maintenance, (at least 2 of 3 treatments) administered on a schedule similar to the SWOG 8507 study regimen.
• All clinical, intra-operative and pathological items for the AUA risk stratification must be documented. This includes bladder mapping, according to the instructions specified in the protocol. With regard to BCG and/or other NMIBC treatments documentation must include:
• Date of initial treatment,
• Date of last treatment,
• The number of courses administered and the number of treatments administered in each course.
• Patients with concomitant papillary tumor(s) must have undergone a repeat TUR 2-4 weeks prior to the first study treatment:
• if the previous TUR was incomplete,
• if there was no muscle in the specimen after the initial TUR (except in TaLG tumors),
• in all T1,
• in all HG tumors ≥ 3cm.
• CT-IVU or MRI-IVU or IVU/retrograde confirmation of absence of tumor(s) in the upper tract, kidney and ureters performed within 6 months before the study treatment initiation, in selected cases, as recommended in latest AUA guidelines published prior to screening. If IVU/retrograde protocol is not available or contrast allergy/poor renal function preclude such imaging, then non-contrast CT or MRI of the abdomen/pelvis within the same timeframe will suffice.
• Visual inspection to exclude urothelial carcinoma (UC) in the urethra during cystoscopy.
• Biopsy of the prostatic urethra, prior to enrollment, to exclude UC of the prostatic urethra, in male patients with:
• tumor of trigone,
• tumor of bladder neck, or

You may not qualify if:

• Non-UC tumor of the urinary tract.
• Upper tract and/or intramural tumors (e.g., in ostium).
• Positive selective cytology from the upper tract.
• History of stage \> T1 UC.
• Papillary tumors \> T1 in repeat TUR.
• Known or suspected reduced bladder capacity. Patients will have an ultrasonic estimation of maximum bladder capacity or void spontaneously the maximum they can retain in their bladder, and this will be used to determine urine volume. A minimum volume of 250 ml is required.
• Patients with severe bladder outlet obstruction not adequately controlled with medication (AUA symptom score ≥ 20).
• Bleeding disorder.
• Gross hematuria within the past 2 weeks before treatment start.
• Lactating women.
• Women of childbearing potential unwilling or unable to use adequate contraception if sexually active.
• More than low-dose methotrexate (\>17.5 mg once a week).
• Other malignancy within the past 5 years, except: non melanomatous skin cancer cured by excision, surgically treated carcinoma in situ of the cervix or ductal CIS (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active surveillance or hormone control) with a life expectancy of more than 5 years.
• Any known allergy (e.g., to MMC) or adverse event that would prevent a prospective study participant from receiving the study treatment.
• Known untreated urethral strictural disease or bladder neck contracture or any other condition that may prevent catheterization with a 21F catheter. Patients may undergo dilation or urethral incision before entering the study.

Sponsors & Collaborators

• Medical Enterprises Ltd.: lead

Study Sites (4)

Chesapeake Urology Research Associates

Hanover, Maryland, 21076, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Disease

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael A O'Donnell, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 7, 2017
• Study Start: April 4, 2019
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: April 15, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)