Condition category
Cancer
Date applied
16/04/2009
Date assigned
27/05/2009
Last edited
11/06/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.idm-pharma.com

Contact information

Type

Scientific

Primary contact

Prof Maximilian Burger

ORCID ID

Contact details

Oberarzt
Klinik für Urologie
Universität Regensburg
Landshuterstr. 65
Regensburg
93053
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MAK-BLA-202

Study information

Scientific title

Phase II/III, multicentre, open-label, randomised study comparing autologous intravesical macrophage cell therapy (Bexidem®) to intravesical Bacillus Calmette-Guerin (BCG) therapy in patients with superficial papillary bladder cancer who have undergone complete transurethral resection

Acronym

Bexidem®

Study hypothesis

1. Phase II step:
1.1. Primary objective: To demonstrate a superior safety profile of Bexidem® therapy with respect to 'frequent immunotherapy-linked adverse events' (FILAEs) compared to BCG therapy
1.2. Secondary objective: To evaluate overall efficacy and recurrence-free survival in patients treated with Bexidem® therapy

2. Phase III step:
2.1. Primary objective: To compare efficacy (recurrence-free survival) of Bexidem® therapy to BCG therapy
2.2. Secondary objective: To evaluate overall safety of Bexidem® therapy as compared to BCG therapy

Ethics approval

All participating centres received ethics approval prior to recruitment of the first participant:
1. Spain: Regional EC - CEIC Regional de la Comunidad de Madrid; Local EC - CEIC Autonomico de Ensayos Clinicos de Andalucia - Consejeria de Salud; Local EC - Comité Etico de Investigacion Clinica de Galicia SERGAS
2. Hungary: Central EC Central Ethics Committee - Egészségügyi és Tudományos Tanács; Institutional Research Ethic Committee - Fövàrosi Szent Istvàn Hospital; Institutional Research Ethic Committee - Budai Irgal Masrendi Intézményi Kutatàsetikai Bizottsàg; IKEB Hatarozat dön tésröl; Regionalis Kuratasetukai Bizottsaga (Györ - Moson - Sopron etc..) - Egészségügyi és Tudományos Tanács; Local Ethic Committee Bajcsy - Zsilinszky Hospital; Regional and Institutional Committee of Science and research Ethics - Semmelweis Hospital; Local Ethic Committee Jahn Ferenc South-Pest Hospital; Regionalis Kuratasetukai Bizottsaga (Györ - Moson - Sopron etc..) - Egészségügyi és Tudományos Tanács; Institutional Research Ethic Committee of lcal Government of Capital City; Local Ethic Committee Bàcs - Kiskun County Hospital
3. France: Central EC - CCPPRB du l'Hopital Paris
4. Germany: Ethik-Kommission Medizinische - Fakultät Universität Regensburg; Ethikkommission Med. Fakultät der HHU Düsseldorf; Ethikkommission Charité - Universitätsmedizin; Ethikkommission - Medizinischen Fakultät der Technischen Universität; Ethikkommission der Landesärztekammer Rheinland-Pfalz
5. Belgium: Commission d'Ethique Biomédicale - Hospitalo-Facultaire; Comité Éthique - CHR de la Citadelle; Etisch Comité O.L. Vrouwziekenhuis; Etisch Comité AZ Groeninge
6. Luxembourg: Comité Éthique CNER 18

Study design

Phase II/III multicentre open-label randomised study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Superficial papillary bladder cancer

Intervention

Dosage and administration:
Three treatment cycles: first cycle consists of either 6 weekly Bexidem® instillations (0.5 - 2 x 10^8 cells in a total volume of 50 ml per instillation) or BCG instillations (1 - 19.2 x 10^8 CFU in a total volume of 50 ml). Maintenance consists of two cycles (at month 3 and month 6) of each three weekly Bexidem® instillations, or 3 weekly BCG instillations.

Study duration:
Phase II: Individual patient participation: 24 months including follow-up observation. Total study duration: 42 months
Phase III: Individual patient participation: 24 months including follow-up observation. Total study duration: dependent upon total number of patients

Intervention type

Drug

Phase

Phase II/III

Drug names

Bexidem®

Primary outcome measures

Phase II: To demonstrate a superior safety profile of Bexidem® with respect to FILAEs compared to BCG therapy.
Phase III: To compare efficacy (recurrence-free survival) of Bexidem® therapy to BCG therapy.

The comparison of toxicity will be performed after all patients in the Phase II step have completed all cycles of treatment and at least three months of follow up (month 9). The recurrence-free survival in each group will be estimated after all Phase II patients have completed at least six months of follow up after the last treatment (month 12 visit). These analyses will serve as the basis for a decision to proceed to the Phase III step as well as to estimate the expected recurrence-free survival in the two groups and recalculate the sample size required for the Phase III step.

Secondary outcome measures

Phase II: To evaluate overall efficacy and recurrence-free survival in patients treated with Bexidem® therapy.
Phase III: To evaluate overall safety of Bexidem® therapy as compared to BCG.

The comparison of toxicity will be performed after all patients in the Phase II step have completed all cycles of treatment and at least three months of follow up (month 9). The recurrence-free survival in each group will be estimated after all Phase II patients have completed at least six months of follow up after the last treatment (month 12 visit). These analyses will serve as the basis for a decision to proceed to the Phase III step as well as to estimate the expected recurrence-free survival in the two groups and recalculate the sample size required for the Phase III step.

Overall trial start date

25/06/2004

Overall trial end date

16/03/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male and female patients
2. At least 18 years of age
3. Fully resected papillary transitional cell carcinoma
4. Stage TaGI, TaGII, TaGIII, T1GI or T1GII (N0, M0)
5. Either of the following:
5.1. Plurifocal tumours
5.2. Unifocal tumour provided greater than or equal to two tumour occurrences within the last 24 months
6. World Health Organization (WHO) performance status 0 - 2
7. Normal upper urinary tract as documented by intravenous (IV) urography or computed tomography (CT) scan
8. Blood creatinine less than 200 umol/L
9. Alanine aminotransferase (ALT) and aspartate aminotrasferase (AST) less than 2.5 x upper limit of normal (ULN)
10. Leukocytes greater than or equal to 3,500/mm^3
11. Able to understand and follow treatment scheme
12. Signed and dated Informed Consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Phase II: 138 patients (69 per arm); up to 512 additional patients for phase III

Participant exclusion criteria

1. Greater than or equal to T1GIII bladder cancer
2. Carcinoma in situ (CIS)
3. Active tuberculosis
4. Other active infection (including urinary tract infection) and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B or hepatitis C infection
5. History of other active malignancy within five years, except adequately treated basal cell and squamous cell carcinoma of the skin
6. Other serious illness or medical conditions (e.g. history of significant cardiac or respiratory dysfunction)
7. Patients with a contra-indication preventing apheresis
8. History of autoimmune-related disorder
9. Known hypersensitivity to any of the components of the study drugs (e.g. dimethylsulphoxide [DMSO])
10. Immunosuppression or congenital or acquired immune deficiencies, whether due to concurrent disease (e.g. acquired immune deficiency syndrome [AIDS], leukaemia, lymphoma), cancer therapy (cytotoxic drugs, radiotherapy) or immunosuppressive therapy (e.g. corticosteroids, cyclosporin)
11. Family history of Creutzfeldt-Jacob disease and/or risk of Creutzfeldt-Jacob disease defined as patient having received extracted growth hormone or neurosurgery before 1996
12. Prior systemic reaction to BCG therapy
13. Pregnant or nursing women

Recruitment start date

25/06/2004

Recruitment end date

16/03/2007

Locations

Countries of recruitment

Belgium, France, Germany, Hungary, Luxembourg, Spain

Trial participating centre

Oberarzt
Regensburg
93053
Germany

Sponsor information

Organisation

IDM Pharma SA (France)

Sponsor details

172 rue de Charonne
Paris Cedex 11
75545
France

Sponsor type

Industry

Website

http://www.idm-pharma.com

Funders

Funder type

Industry

Funder name

IDM Pharma SA (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20529333

Publication citations

  1. Results

    Burger M, Thiounn N, Denzinger S, Kondas J, Benoit G, Chapado MS, Jimenz-Cruz FJ, Kisbenedek L, Szabo Z, Zsolt D, Grimm MO, Romics I, Thüroff JW, Kiss T, Tombal B, Wirth M, Munsell M, Mills B, Koh T, Sherman J, The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial., J Transl Med, 2010, 8, 54, doi: 10.1186/1479-5876-8-54.

Additional files

Editorial Notes