Intravesical Mistletoe Extract in Superficial Bladder Cancer: A Phase III Efficacy Study

INTRODUCTION

  • Org Study ID: AB03
  • Secondary ID: 2013-003446-16
  • NTC ID: NCT02106572
  • Sponsor: Abnoba Gmbh

BRIEF SUMMARY


The aim of this phase III study is to assess the efficacy of abnobaVISCUM® 900 compared with
Mitomycin C (MMC) monotherapy in patients with superficial bladder carcinoma by evaluation of
the time to tumor recurrence. Secondary objective is to evaluate the safety of abnobaVISCUM®
900, in particular, to compare the toxicity of the two treatments. Another secondary
objective is the treatment efficacy as measured by calculated prognosis for recurrence and
progression after 1 year, the tumor grading in case of a recurrence and by measurement of
Quality of Life.

DETAILED DESCRIPTION


This is a randomized, open-label, active-controlled, prospective, multinational Phase III
confirmative study with 2 treatment groups and an adaptive design (Bauer and Köhne, 1994).
The study is designed to compare the efficacy of treatment with abnobaVISCUM® 900 with
Mitomycin C (MMC). Patients with completely resected superficial bladder carcinoma (Stage Ta)
with an intermediate risk classification according to the European Association of Urology
(EAU, update 2013) and with one immediately post operative MMC 40 mg intravesical
instillation will be eligible for inclusion in the study.

The study comprises a screening period of not more than 6 weeks, a treatment period of 12
months for abnobaVISCUM® 900 and MMC and a follow-up period of 12 months. Patients will be
screened within 6 weeks after the transurethral resection of the bladder (TURB) and the
immediately post operative MMC 40 mg intravesical instillation. A re-resection should be
performed before inclusion if indicated. Every patient is to provide written informed consent
before any study related procedures will be performed.


  • Overall Status
    Recruiting
  • Start Date
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Time to tumor recurrence

Primary Outcome 1 - Timeframe: up to two years

CONDITION

  • Superficial Bladder Cancer

ELIGIBILITY


Inclusion Criteria:

- Signed and dated written informed consent for data protection and willingness to
participate and comply with the study protocol prior to any study-related procedures

- Completely resected (detrusor muscle in the TUR specimen according to need)
superficial bladder carcinoma (Stage Ta) with classification as intermediate-risk
according to the EAU (update 2013) and one immediately post operative intravesical MMC
instillation of 40 mg, completed re-resection if indicated

- Karnofsky Performance Status of 50% to 100% (corresponding to Eastern Cooperative
Oncology Group (ECOG) Performance Status of 0 to 2)

- Life expectancy of ≥ 2 years at the time point of study inclusion

- Normal renal and liver function, normal cardiac and hematology profiles (patients with
laboratory values slightly outside the reference range may be included, unless the
investigator considers the abnormality as clinically significant)

- Female patients of childbearing potential must have a negative pregnancy test (β-human
chorionic gonadotropin test) at Screening. Pregnancy during the treatment period
including 12 weeks after the last instillation has to be excluded

Exclusion Criteria:

- Locally infiltrative or metastatic bladder tumor (Stage T2 or greater), low-risk Ta
tumor (primary, solitary, LG/G1, <3 cm, no CIS) or high-risk tumors according to EAU
classification, update 2013 (T1; HG/G3; CIS; multiple and recurrent and large [>3 cm]
Ta G1/G2 tumors [all conditions must be present at this point], presence of upper
urinary tract tumors or lesions which were not completely removed by TURB

- Urinary tract infection, benign prostatic obstruction grade II or III, neurogenic
bladder, stress incontinence, bladder or urethral diverticula, fistulas or urethral
stenosis

- Patients with acute systemic illness, such as inflammatory infections with fever >
38°C

- Patients with previous recurrence of a superficial bladder cancer or radiotherapy of
the bladder or other intravesical treatment within the last 6 months, or patients with
previous mistletoe therapy

- Patients with other previous or co-existing malignancies or CIS

- Patients having any previous or concurrent therapy with a systemic chemo- /
immunotherapeutical treatment regimen, in particular vinca alkaloids, bleomycine and
doxorubicine, or patients who are treated with pyroxidine hydrochloride (vitamin B6)

- Untreated coagulation disorders or inadequate anticoagulation therapy

- Leukocyte count < 4,000/mm3 or platelet count < 100,000/mm3

- Serum creatinine > 1.7 mg/dL

- Patients with known hypersensitivity to the excipients of the study medication
(monosodium phosphate, disodium phosphate, ascorbic acid)

- Patients with a known hypersensitivity to mistletoe products and MMC

- Patients who were administered within a 4-week period before Visit 1 any other
experimental drug under investigation

- Male patients planning to father a child or sperm donation from the first
administration of study medication until 3 months after the last administration of the
study medication

- Male patients unwilling to use barrier contraception ie, condoms and spermicide, from
the day of first administration of the study medication until 12 weeks after
administration of the study medication. In case the sexual relation is restricted to
women fulfilling one of the criteria listed under inclusion criteria for female
patients the barrier contraception is not necessary.

- Patients with a history of alcohol and / or drug abuse

- Patients who are unable to be regularly observed, not permitting adequate follow-up
and compliance to the protocol

Gender: All

Minimum Age: 85 Years

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Stephan Tschirdewahn, Dr.

Role: Principal Investigator

Affiliation: Senior Physician of the Urological Clinic of the University Hospital Essen

Overall Contact

Name: Stephan Tschirdewahn, Dr.

Phone: +49 7231 315050

Email: eisenbraun@abnoba.de

LOCATION

Facility Status Contact
Facility: Theodor Bilharz Research Institute
Giza, 12411
Egypt
Status: Recruiting Contact:
Tarek El Leithy, Prof. Dr.
+2 01222117206
Facility: Universitätsklinikum Freiburg
Freiburg, Breisgau 79106
Germany
Status: Recruiting Contact:
Wolfgang Schultze-Seemann, Prof. Dr.
+49 761 27028920
Facility: Kliniken Nordoberpfalz AG, Klinikum Weiden
Weiden, Oberpfalz 92637
Germany
Status: Recruiting Contact:
Thoeodor Klotz, Prof. Dr.
+49 0961 3033302
Facility: Urologisches Zentrum Euregio
Aachen, 52064
Germany
Status: Recruiting Contact:
Jörg Horstmann, Dr.
+49 0241 33 988
Facility: Urologische Praxis
Berlin, 10711
Germany
Status: Recruiting Contact:
Frank Christoph, PD Dr.
+49 30 8915025
Facility: Urologische Gemeinschaftspraxis
Berlin, 13187
Germany
Status: Recruiting Contact:
Roger Zillmann, Dipl.-Med.
+49 30 4853868
Facility: Urologische Praxis Bonn-Rhein-Sieg
Bonn, 53177
Germany
Status: Recruiting Contact:
Reinhold Schaefer, Dr.
+49 228 957370
Facility: Urologicum Duisburg
Duisburg, 47179
Germany
Status: Recruiting Contact:
Andreas Swoboda, Dr.
+49 203 50030420
Facility: Urologische Praxis
Eisleben Lutherstadt, 06295
Germany
Status: Recruiting Contact:
Ralf Eckert, Dr.
+49 3475 250059
Facility: Überörtliche urologische Gemeinschaftspraxis
Erkrath, 40699
Germany
Status: Recruiting Contact:
Wolfgang Rulf, Dr.
+49 2104 43048
Facility: Clinic of Urology of the University Hospital of Essen
Essen, 45122
Germany
Status: Recruiting Contact:
Stephan Tschirdewahn, Dr.
+49 201 7233210
Facility: Klinik für Urologie, Kinderurologie und Urologische Onkologie - St. Antonius Hospital Gronau
Gronau, 48599
Germany
Status: Recruiting Contact:
Mustapha Addali, Dr.
+49 02562 915 2100
Facility: Urologische Praxis
Hagenow, 19230
Germany
Status: Recruiting Contact:
Wolfgang Warnack, Dr.
+49 0173 9887495
Facility: Urologikum Hamburg
Hamburg, 22399
Germany
Status: Recruiting Contact:
Henrik Suttman, PD Dr.
+49 40 6921440
Facility: Urologische Gemeinschaftspraxis
Heinsberg, 52525
Germany
Status: Recruiting Contact:
Aloys Lappenküper
+49 2452 3113
Facility: Urologische Praxis
Herzberg, 37412
Germany
Status: Recruiting Contact:
Thorsten Werner, Dr.
+49 5521 71212
Facility: Universitätsklinikum Jena
Jena, 07747
Germany
Status: Recruiting Contact:
Marc-Oliver Grimm, Prof. Dr.
+49 3641 935206
Facility: Urologische Praxis
Karlsruhe, 76133
Germany
Status: Recruiting Contact:
Michael Rug, Dr.
+49 721 22080
Facility: Urologische Gemeinschaftspraxis
Kempen, 47906
Germany
Status: Recruiting Contact:
Jan Marin, Dr.
+49 2152 899290
Facility: Urologische Gemeinschaftspraxis
Kirchheim unter Teck, 73230
Germany
Status: Recruiting Contact:
Robert Rudolph, Dr.
+49 7021 3200
Facility: Urologische Facharztpraxis Cologne-Study-Group
Köln, 50968
Germany
Status: Recruiting Contact:
Jörg Klier, Dr.
+49 221 362025
Facility: Urologische Praxis
Langenfeld, 40764
Germany
Status: Recruiting Contact:
Eberhard Mumperow, Dr.
+49 2173 82426
Facility: Urologische Gemeinschaftspraxis
Leipzig, 04229
Germany
Status: Recruiting Contact:
Detlef Nietzsch, Dr.
+49 0341 4533-80
Facility: Universitätsklinikum Gießen und Marburg GmbH Klinik für Urologie und Kinderurologie
Marburg/Lahn, 35033
Germany
Status: Recruiting Contact:
Axel Hegele, Prof. Dr.
+49 6421 5862575
Facility: Urologische Praxis
Marburg, 35039
Germany
Status: Recruiting Contact:
Maren Schwickardi, Dr.
+49 6421 96440
Facility: Urologische Facharztpraxis
Markkleeberg, 04416
Germany
Status: Recruiting Contact:
Matthias Schulze, Dr.
+49 341 3542755
Facility: Urologische Gemeinschaftspraxis
Michelstadt, 64720
Germany
Status: Recruiting Contact:
Alwin Weber, Dr.
+49 6061 925777
Facility: Urologische Gemeinschaftspraxis
Mühlacker, 75417
Germany
Status: Recruiting Contact:
Armin Weigl, Dr.
+49 7041 5622
Facility: Urologische Gemeinschaftspraxis
Mülheim, 45468
Germany
Status: Recruiting Contact:
Tim Schneider, Prof. Dr.
+49 208 94067900
Facility: Privatärztliche urologische Studienpraxis
Nürtingen, 72622
Germany
Status: Recruiting Contact:
Susan Feyerabend, Dr.
+49 170 3809233
Facility: Urologische Gemeinschaftspraxis - URONEUM
Reutlingen, 72764
Germany
Status: Recruiting Contact:
Simone Maier, Dr.
+49 07121 694980
Facility: Urologische Gemeinschaftspraxis
Wesel, 46483
Germany
Status: Recruiting Contact:
Andreas Stammel, Dr.
+49 281 4755590
Facility: Urologische Praxisgemeinschaft
Wolfsburg, 38440
Germany
Status: Recruiting Contact:
Jens Telle, Dipl.-Med.
+49 05361 3769980
Facility: Urologische Facharztpraxis
Würselen, 52146
Germany
Status: Recruiting Contact:
Thomas Pulte, Dr.
+49 2405 452680