Clinical trial NCT02007005: Maximum Tolerable Concentration of abnobaVISCUM Fraxini Intravesically in Patients With Superficial Bladder Cancer
Official title: Dose-Escalation-Study With abnobaVISCUM® Fraxini 2 (AVF2) as Intravesical Instillation in Patients With Superficial Bladder Cancer According to ICH/GCP (International Conference on Harmonisation/Good Clinical Practice) - Guidelines: a Phase Ib/IIa Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Superficial Bladder Cancer
Keywords: superficial bladder cancer
mistletoe extract
maximum tolerated dose
marker tumor
remission
recurrence rate
Lead sponsor: Abnoba Gmbh
Sponsor class: INDUSTRY
First posted: 2013-12-10
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this phase Ib/IIa study is to investigate the maximum tolerable concentration of abnobaVISCUM® Fraxini for intravesical instillation in patients with superficial bladder cancer. Secondary objectives are the local and systemic tolerability, the influence on tumor remission and the influence on the one-year recurrence rate.

Detailed description: A dose-escalation-study according ICH/GCP (International Conference on Harmonisation/Good Clinical Practice) with different concentrations of abnobaVISCUM® Fraxini is conducted in two hospitals in Germany and Egypt. Patients with superficial bladder cancer TaG1/G2 or T1G1/G2 are enclosed after TUR-B (transurethral resection bladder). The tolerability of the different concentrations is assessed after weekly instillations into the urinary bladder for 6 weeks. A direct antitumoral effect is assessed on a single marker tumor left in the bladder after a complete TUR of all other lesions according a study design established by the EORTC-GENITO-URINARY GROUP (European Organisation for Research and Treatment of Cancer). A re-TUR is conducted after 12 weeks. Tumor response is measured by biopsy of the marker lesion and by cytology. Safety of the instillations is measured by analysis of adverse events, vital signs and clinical laboratory tests. After treatment of a cohort is finished a safety evaluation is conducted to decide about the increase to the next dosage.

Eligibility criteria: Inclusion Criteria:

* Patients with clinically proved superficial bladder cancer (Ta G1/G2 or T1G1/G2) 2 - 7 weeks before transurethral resection
* Written informed consent for study participation and for documentation of disease data including further distribution of these data

Exclusion Criteria:

* Muscle invasive bladder carcinoma and/or carcinoma in situ (CIS)
* Intravesical instillation therapy within 6 months prior to study enrolment
* Radiotherapy of the bladder prior to study enrolment
* Contracted bladder (capacity less than 100 ml)
* Non treated acute or chronic urinary tract infection
* Allergy against mistletoe extract preparations
* Subvesical obstructions (e. g. prostate hyperplasia, urethral stenosis, residual urine volume more than 80 ml)
* Severe illnesses and circumstances not permitting study participation (e. g. alcoholism or substance abuse)
* Pregnancy or lactation (pregnancy test if required) as well as women without sufficient contraception
* Participation in another clinical study within 30 days prior to this study
* Administration of immunotherapeutic and/or cytostatic drugs within 4 weeks prior to study enrolment
* Chronic progressive infections (e. g. tuberculosis)
* Pre-treatment with mistletoe extracts/mistletoe lectins

Primary outcomes:
measure: Maximum tolerable concentration of abnobaVISCUM Fraxini for intravesical instillation
timeFrame: 6 weeks
Secondary outcomes:
measure: Local and systemic tolerability of different concentrations of abnobaVISCUM Fraxini for intravesical instillation
timeFrame: 6 weeks
measure: Influence on remission and influence on the one year recurrence rate of abnobaVISCUM Fraxini for intravesical instillation
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Giza
country: Egypt
facility: Theodor Bilharz Research Institute
city: Essen
country: Germany
facility: Clinic of Urology of the University Hospital of Essen
Study officials:
affiliation: Director of the Urological Clinic of the University Hospital Essen
name: Herbert Ruebben, Prof.Dr.Dr.
role: STUDY_DIRECTOR
References:
citation: Rose A, El-Leithy T, vom Dorp F, Zakaria A, Eisenhardt A, Tschirdewahn S, Rubben H. Mistletoe Plant Extract in Patients with Nonmuscle Invasive Bladder Cancer: Results of a Phase Ib/IIa Single Group Dose Escalation Study. J Urol. 2015 Oct;194(4):939-43. doi: 10.1016/j.juro.2015.04.073. Epub 2015 Apr 22.