SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I

NCT02254915 | Withdrawn Phase 3 DMC

• 1 other identifier: CLN-002-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A multi-institutional, prospective, randomised, open-label, superiority, comparative, active-controlled, phase 3 study. The study will compare Synergo RF-induced hyperthermia-chemotherapy (SHTC) plus mitomycin C (MMC) to standard treatment of bacillus Calmette-Guérin (BCG) therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC, and will evaluate recurrence and progression rate over two years of follow-up.

Conditions

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases

Keywords

Synergo; RITE; SHTC; Non Muscle Invasive Bladder Cancer; NMIBC; Superficial Bladder Cancer; Urothelial Cell Cancer; Transitional Cell Cancer; Mitomycin

Outcome Measures

Primary Outcomes (1)

• RFS time

  The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).

  2 years

Secondary Outcomes (7)

• Progression-free survival time

  2 years

• Recurrence free survival time by risk group

  2 years

• Organ preservation rate

  2 years

• Overall survival time

  2 years

• Disease-specific survival time

  2 years

Study Arms (2)

Synergo + MMC

EXPERIMENTAL

Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy (SHTC) with mitomycin C (RITE) intravesical therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,

Device: Synergo + MMC

Bacillus Calmette-Guérin

ACTIVE COMPARATOR

Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,

Drug: Bacillus Calmette-Guérin

Interventions

Synergo + MMC DEVICE

Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy with mitomycin C (RITE). Intravesical instillation of MMC utilizing the Synergo system.

Also known as: RITE, SHTC

Synergo + MMC

Bacillus Calmette-Guérin DRUG

Intravesical instillation of BCG.

Also known as: BCG

Bacillus Calmette-Guérin

Eligibility Criteria

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

You may qualify if:

• Patients with primary intermediate or high-risk papillary NMIBC according to the EAU Guidelines and intermediate and high-risk recurrences that have not received BCG within the previous 2 years or chemotherapy treatment (apart from one early instillation) within the previous year.
• All clinical, intra-operative and pathological items for the EAU risk stratification must be documented including a bladder map.
• Patients must have undergone a re-resection (second TURB in accordance with the EAU Guidelines) (i) if the initial TURB was incomplete (ii) if there was no muscle in the specimen after the initial TURB (except in TaG1/LG tumours) (iii) in all T1 and all G3/HG tumours TURB of T1 sites must include muscle. Re-resection must be negative in patients diagnosed with T1 and/or G3/HG and/or multiple tumours in the initial TURB.
• No UC in the upper tract, kidney and ureters. This should be confirmed by CT-IVU or IVU performed at time of initial diagnosis in selected cases as recommended in latest EAU guidelines published prior to screening.
• No UC in the urethra, excluded by visual inspection during cystoscopy and, in addition, in patients with (i) tumour of trigone (ii) tumour of bladder neck (iii) abnormal prostatic urethra UC must be excluded by biopsy of the prostatic urethra in all male patients or, in female patients, from the portion of the urethra adjacent to the bladder neck, before study recruitment.
• All patients must have urine cytology dated within the screening period prior to randomisation.
• Age ≥ 18 yrs
• Normal kidneys and ureters.
• Pre-treatment haematology and biochemistry values within acceptable limits:
• (i) haemoglobin ≥ 10 g/dl (g/100 ml) (ii) platelets ≥ 150 x 109/L (103/mm3) (iii) WBC ≥ 3.0 x 109/L (103/mm3) (iv) ANC ≥ 1.5 x 109/L (103/mm3, absolute neutrophil count) (v) Serum creatinine, SGOT, SGPT, Alkaline phosphatase: \< 1.5 x UNL (upper normal limit)
• Negative pregnancy test for women of child-bearing potential
• A life expectancy at least of the duration of the trial.
• Unfit or unwilling to have a full or partial cystectomy.
• Signed informed consent.

You may not qualify if:

• UC involving the prostatic urethra
• Non-UC tumour of the urinary tract
• Upper tract and intramural tumours (e.g. in Ostium).
• History of stage \> T1 UC.
• CIS (suspected or present).
• Known or suspected reduced bladder capacity. Patients will have a US 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.
• Bleeding disorder
• Macrohaematuria of ≥ 250 RBC's/uL or equivalent (e.g. \> "+++" erythrocytes in a dipstick analysis).
• Pregnant or lactating women.
• Women of childbearing potential unwilling or unable to use adequate contraception if sexually active.
• More than a maintenance dose of oral corticosteroids (maintenance dose defined as the same dose regimen over the past 6 months for a condition requiring continual corticosteroid treatment) or patients with an immuno-compromised state for any reason.
• More than low-dose Methotrexate (\>17.5 mg once a week).
• Other malignancy within the past five years, except: non-melanomatous skin cancer cured by excision, adequately 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 or adverse event that would prevent them from receiving a treatment that they may be randomised to within the trial.
• Known untreated strictural disease or bladder neck contracture or any other condition that may prevent catheterisation with 21F catheter. Patients may undergo dilation or urethral incision before entering the study.

Sponsors & Collaborators

• Medical Enterprises Europe B.V.: lead

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Igal Ruvinsky, PhD

  Medical Enterprises Europe B.V.

  STUDY DIRECTOR

• Gerson Luedecke, Dr. med.

  Universitätsklinikum Gießen und Marburg

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 2, 2014
• Primary Completion: January 1, 2020
• Last Updated: April 1, 2015

Record last verified: 2015-03