Intravesical Mistletoe Extract in Superficial Bladder Cancer: A phase III efficacy study (TIM) - TIM

Phase 1

• Conditions: Male and female patients aged = 18 to < 80 years with a completely resected superficial bladder cancer (Stage Ta and T1 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.; MedDRA version: 20.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003446-16-DE
• Lead Sponsor: Abnoba GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-04-29
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 546

Inclusion Criteria

Patients may be included in the study only if they meet all of the following criteria:
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 < 80 years
4. Completely resected (detrusor muscle in the TUR specimen has to be present) superficial bladder carcinoma (Stage Ta or T1) with classification as intermediate-risk according to the EAU (without CIS and/or G3) and one immediately post operative intravesical MMC instillation of 40 mg, completed re-resection 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 (ß-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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 182
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 364

Exclusion Criteria

Patients will not be entered in the study if they meet at least one of the following criteria:
1. Have locally infiltrative or metastatic bladder tumor (Stage T2 or greater), low-risk or high-risk Stage Ta and T1 tumors (according to EAU classification), a bad prognosis regarding progression (CIS or G3), 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
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
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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified