Efficacy of Intravesical Extract of Fresh Ash Mistletoe Herb Versus Mitomycin C in Intermediate-Risk Superficial Bladder Carcinoma
- Trial ID
- 2023-503718-66-00
- Protocol
- Study-AB03
- Sponsor
- Abnoba GmbH
Trial statistics
Objectives
The primary objective of this study is to assess the **efficacy** of abnobaVISCUM® 900 compared with Mitomycin C (MMC) monotherapy in patients with superficial bladder carcinoma. The primary efficacy criterion is the time to tumor recurrence, which is clinically relevant as it directly impacts patient prognosis and treatment planning.
Secondary objectives include evaluating the **safety** of abnobaVISCUM® 900 compared to MMC monotherapy, with a particular focus on comparing the toxicity profiles of the two treatments. Additionally, the study aims to assess treatment efficacy through calculated prognosis for recurrence and progression after one year, tumor grading, and Quality of Life. These secondary objectives are crucial for understanding the overall benefit-risk profile of abnobaVISCUM® 900 in this patient population.
Participants
The clinical trial involves a total of **26 participants**, comprising both **male and female** patients. The study population includes individuals aged **18 to 85 years** who have been diagnosed with completely resected superficial bladder cancer, specifically Stage Ta tumors classified as intermediate-risk according to the European Association of Urology (EAU) guidelines. Participants have undergone a transurethral resection of the bladder (TURB) and received one immediate post-operative intravesical instillation of either Mitomycin C (MMC) or epirubicin. The trial population was selected based on specific health criteria, including a **Karnofsky Performance Status** of 50% to 100%, a life expectancy of at least two years, and normal renal, liver, cardiac, and hematology profiles. Female participants of childbearing potential are required to have a negative pregnancy test and must use effective contraception. The study does not include a vulnerable population, and participants are expected to comply with the study protocol. The sponsor has not provided information on lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **abnobaVISCUM** compared to **Mitomycin C** (MMC) monotherapy in patients with superficial bladder carcinoma. This is a Phase III, randomized, double-blind, controlled study. The primary endpoint is the time to tumor recurrence, with secondary endpoints including safety, toxicity, tolerability, and quality of life assessments. The trial is expected to run until June 2028, with participant recruitment having commenced in March 2015.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and medical history. The inclusion criteria require participants to be aged 18 to 85 years, with completely resected superficial bladder carcinoma classified as intermediate-risk. They must have a life expectancy of at least two years and normal renal, liver, cardiac, and hematology profiles. Female participants of childbearing potential must have a negative pregnancy test and use effective contraception.
Following the screening visit, participants will be randomized to receive either the investigational product, abnobaVISCUM, or the comparator, MMC, both administered via intravesical use. The maximum treatment period is 48 weeks. Regular follow-up visits will be conducted to monitor the participants' health status, assess adverse events, and evaluate the efficacy of the treatment. These visits will include laboratory assessments and quality of life questionnaires.
The end-of-study visit will occur after the completion of the treatment period or upon early termination. Participants may be withdrawn from the study if a recurrence of bladder carcinoma is recorded, or if they experience significant adverse events that compromise their safety. The expected length of participant involvement is up to 48 weeks, with conditions for early termination including tumor recurrence or intolerable side effects.
Treatment
The clinical trial involves the administration of **abnobaVISCUM Fraxini 20 mg** solution for injection, which contains the active substance **extract of fresh ash mistletoe herb**. This investigational medicinal product is provided in a sealed 10 ml glass ampoule containing 9 ml of solution. The maximum daily dose is 45 ml, with a total maximum dose of 675 ml over a treatment period of 48 weeks. The solution is administered via **intravesical use**. The product is classified as an anthroposophic medicinal product and is manufactured by ABNOBA GMBH. The primary packaging differs from the marketed product due to a larger volume, but this does not affect the product's stability.
The comparator treatment in this study is **Mitomycin**, a cytotoxic antibiotic provided as an intravesical solution or solution for injection. The active substance is **mitomycin**, and the maximum daily dose is 40 mg, with a total maximum dose of 400 mg over the same 48-week treatment period. Mitomycin is also administered via **intravesical use**. This product serves as the standard-of-care therapy against which the efficacy of abnobaVISCUM Fraxini is being compared. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol.
Efficacy
The efficacy of the investigational product, abnobaVISCUM® 900, will be assessed in a Phase III clinical trial comparing its effects to Mitomycin C (MMC) monotherapy in patients with superficial bladder carcinoma. The primary efficacy endpoint is the **time to tumor recurrence**. This parameter will be measured by monitoring patients for any recurrence of bladder carcinoma, at which point they will be withdrawn from the study treatment. Secondary efficacy endpoints include prognosis after one year for recurrence and progression, estimated using the European Organization for Research and Treatment of Cancer (EORTC) Bladder Cancer Calculator, tumor grading, and Quality of Life assessments using the EORTC QLQ-C30 and BLS24 questionnaires.
The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the study duration, with the primary endpoint being continuously monitored. The secondary endpoints will be evaluated at designated time points, including one year post-treatment. The study will utilize validated tools and instruments, such as the EORTC Bladder Cancer Calculator and quality of life questionnaires, to ensure accurate and reliable data collection. The trial is designed to provide comprehensive insights into the efficacy of the investigational product in delaying tumor recurrence and improving patient outcomes in superficial bladder carcinoma.
Inclusion and Exclusion Criteria
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
- Male or female outpatients
- Aged ≥ 18 to ≤ 85 years
- 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, see Appendix 4) and one immediately post operative intravesical MMC instillation of 40 mg or Epirubicin 50 mg (only Poland), completed re-resection (without another immediate MMC instillation) if indicated
- Have a Karnofsky Performance Status of 50% to 100% (corresponding to ECOG Performance Status of 0 to 2)
- Have a life expectancy of ≥ 2 years at the time point of study inclusion
- Have 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-HCG test) at screening. All female patients must fulfill one of the following criteria: • Post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with follicle-stimulating hormone (FSH) levels in the laboratory defined post-menopausal range • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation • Sexually active women of childbearing potential must use an effective method of contraception (Pearl-Index < 1, e.g. oral contraceptives, other hormonal contraceptives [vaginal products, skin patches, or implanted or injectable products], or mechanical products such as an intrauterine device or barrier methods [diaphragm, spermicides]) from the time point of signing informed consent until 12 weeks after the last instillation
Exclusion Criteria
- Have 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 (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
- Have 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 (129.6 μmol/l)
- 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 8. 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 27 Mar 2015 | 522 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
abnobaVISCUM Fraxini 20 mg Injektionslösung Wirkstoff: Auszug aus frischem Eschenmistelkraut | Test | INJEKTIONSLÖSUNG | INTRAVESICAL USE | 45 | 48 | PRD777984 |
MITOMYCIN | Comparator | — | INTRAVESICAL USE | 40 | 48 | SUB09006MIG |