The study evaluates the efficacy of the therapy of Mistletoe Extract in patients with superficial bladder cancer. There fore the Mistletoe Extract will be administered directly into the bladder.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abnoba GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Feb 2015 → 24 Apr 2026

Decision date (initial)

2023-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Abnoba GmbH

External identifiers

EU CT number

2023-503718-66-00

EudraCT number

2013-003446-16

ClinicalTrials.gov

NCT02106572

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective of the study is to assess the efficacy of abnobaVISCUM® 900 compared with Mitomycin C (MMC) monotherapy in patients with superficial bladder carcinoma. Primary efficacy criterion will be the time to tumor recurrence.

Secondary objectives 1

1. The secondary objective of the study is to evaluate the safety of abnobaVISCUM® 900 compared to MMC monotherapy in patients with superficial bladder carcinoma, in particular, to compare the toxicity of abnobaVISCUM® 900 compared to MMC monotherapy in patients with superficial bladder carcinoma. Another secondary objective is the treatment efficacy as measured by calculated prognosis for recurrence and progression after 1 year, tumor grading and Quality of Life.

Conditions and MedDRA coding

Male and female patients aged ≥ 18 to ≤ 85 years with a completely resected superficial bladder cancer (Stage Ta tumors) with a classification of intermediate-risk according to the EAU and without CIS and/or G3 tumors after a TURB and one immediately post-operative intravesical instillation of MMC 40 mg or epirubicin 50 mg (only Poland).

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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
2. Male or female outpatients
3. Aged ≥ 18 to ≤ 85 years
4. 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
5. Have a Karnofsky Performance Status of 50% to 100% (corresponding to ECOG Performance Status of 0 to 2)
6. Have a life expectancy of ≥ 2 years at the time point of study inclusion
7. 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)
8. 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 16

1. 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
2. Have urinary tract infection, benign prostatic obstruction grade II or III, neurogenic bladder, stress incontinence, bladder or urethral diverticula, fistulas or urethral stenosis
3. Patients with acute systemic illness, such as inflammatory infections with fever > 38°C
4. 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
5. Patients with other previous or co-existing malignancies or CIS
6. 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)
7. Untreated coagulation disorders or inadequate anticoagulation therapy
8. Leukocyte count < 4,000/mm3 or platelet count < 100,000/mm3
9. Serum creatinine > 1.7 mg/dL (129.6 μmol/l)
10. Patients with known hypersensitivity to the excipients of the study medication (monosodium phosphate, disodium phosphate, ascorbic acid)
11. Patients with a known hypersensitivity to mistletoe products and MMC
12. Patients who were administered within a 4-week period before Visit 1 any other experimental drug under investigation
13. 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
14. 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.
15. Patients with a history of alcohol and / or drug abuse
16. Patients who are unable to be regularly observed, not permitting adequate follow-up and compliance to the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study will be the time to tumor recurrence. Should a recurrence of the bladder carcinoma be recorded, the patient will be withdrawn from study treatment.

Secondary endpoints 2

1. The secondary objective, namely safety including toxicity and tolerability of the study medication, will be assessed by the monitoring of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE), laboratory assessments (hematology, biochemistry and urinalysis) and a global judgment of tolerability.
2. Secondary efficacy endpoints: prognosis after 1 year for recurrence and progression, estimated by the European Organization for Research and Treatment of Cancer (EORTC) Bladder Cancer Calculator, tumor grading, Quality of Life (EORTC QLQ-C30 and BLS24)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abnoba GmbH

Sponsor organisation

Abnoba GmbH

Address

Allmendstrasse 55, Oeschelbronn Oeschelbronn

City

Niefern-Oeschelbronn

Postcode

75223

Country

Germany

Scientific contact point

Organisation

Abnoba GmbH

Contact name

Jürgen Eisenbraun

Public contact point

Organisation

Abnoba GmbH

Contact name

Jürgen Eisenbraun

Third parties 5

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Corrective measures 1 · Art. 77 CTR

Application history

3 submissions — initial application plus substantial / non-substantial modifications