VPM1002BC in Recurrent Non-muscle Invasive Bladder Cancer

NCT02371447 | Completed Phase 1 DMC

• 3 other identifiers: SAKK 06/14SNCTP0000011812014-005330-58
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 16

Brief Summary

This phase I/II trial will assess the safety and efficacy of intravesical instillation of VPM1002BC in patients with recurrent non-muscle invasive bladder cancer after TURB (transurethral resection of the bladder) and standard BCG therapy. In phase I part of the trial, a 3+3 dose de-escalation design will be applied to determine the recommended phase II dose (RP2D). In phase II part of the trial, a maximum of 39 patients will be treated at RP2D to further assess the preliminary efficacy of VPM1002BC.The efficacy and tolerability of VPM1002BC will be compared to results previously reported for BCG in a similar population. The quality of life will be also investigated as a secondary endpoint. Additional immunology assessments are foreseen as exploratory analyses to investigate the immunogenicity of VPM1002BC. The Phase II of the trial has been opened on 27.07.2016.

Conditions

Bladder Cancer

Keywords

bladder cancer; recurrent non-muscle invasive bladder cancer; VPM1002BC; BCG therapy

Outcome Measures

Primary Outcomes (2)

• Phase 1: Dose limiting toxicity (DLT) of intravesical VPM1002BC instillations in patients with recurrence after standard BCG therapy in non-muscle-invasive bladder cancer.

  Adverse events grade 3 and 4 related to the trial treatment

  within 5 weeks

• Phase 2: Recurrence-free rate in the bladder

  No visual evidence of cancer in the bladder and negative cytology.

  at 60 weeks

Secondary Outcomes (6)

• Time to recurrence in the bladder (from registration to tumor recurrence in the bladder)

  within 60 weeks

• Time to recurrence (from registration to recurrence at local, regional or distant site)

  within 60 weeks

• Time to progression (from registration to progression).

  within 60 weeks

• Overall survival calculated from registration until death from any cause

  from registration until death (within 6 years)

• Adverse events assessed according to NCI CTCAE v4.0.

  within 60 weeks

Study Arms (1)

VPM1002BC Induction

EXPERIMENTAL

Phase 1: Induction: 6 intravesical instillations of VPM1002BC in 6-12 weeks (dose de-escalation in cohorts of 3-6 patients) Phase 2: Induction: VPM1002BC at RP2D established in phase I, 6 intravesical instillations in 6-12 weeks (n=39 including patients treated at RPD2 in phase I) Maintenance: 3 instillations of VPM1002BC at months 3, 6 and 12

Drug: VPM1002BC

Interventions

VPM1002BC DRUG

Phase 1: Induction: 6 intravesical instillations of VPM1002BC in 6-12 weeks (dose de-escalation in cohorts of 3-6 patients) Phase 2: Induction: VPM1002BC at RP2D established in phase I, 6 intravesical instillations in 6-12 weeks (n=39 including patients treated at RPD2 in phase I)

Also known as: Mycobacterium bovis BCG∆ureC::Hly+, VPM1002

VPM1002BC Induction

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of recurrent NMIBC (urothelial carcinoma) including repeat TURB confirming tumor-free state of the bladder (confirmed by TURB and biopsy) For patients with pure CIS of the bladder no repeat TURB is necessary.
• Negative cytology before start of treatment, except for patients with concomitant CIS.
• Planned treatment starts 2-5 weeks after last TURB
• Pathological grading includes reporting according to WHO 1973 and 2004.
• One previous cycle of intravesical BCG (induction phase with at least 5 instillations ± maintenance) not more than 5 years ago for NMIBC.
• Patients have recurrent high-risk NMIBC for progression.

You may not qualify if:

• Current or previous ≥ T2 urothelial carcinoma (UC) of the urinary bladder
• Bladder surgery or traumatic catheterization or TURB within 2 weeks prior to the expected start of trial treatment
• Stress urinary incontinence \>I°, severe urge or urge urinary incontinence preventing the patient to keep the IMP in the bladder for at least 1 hour. Residual urinary bladder volume after micturition is \> 150 ml.
• Active concomitant malignant conditions except low risk prostate cancer qualifying for active surveillance according to PRIAS criteria (http://www.prostatecancer-riskcalculator.com/active-surveillance-and-prias-study), basal cell skin carcinoma and cervical carcinoma in situ. History of malignancy in the last 3 years except previous NMIBC.
• Primary or secondary immunodeficiencies
• Positive HIV test
• Chronic administration (defined as more than 14 consecutive days) of immunosuppressive drugs or other immune modifying drugs within three months before instillation
• Uncontrollable urinary tract infection, macroscopic haematuria, suspicion of bladder perforation, urethral strictures (if interfering with trial procedures)
• Current and past pelvic radiation and brachytherapy
• Active tuberculosis or other ongoing mycobacterial infection.
• History of anaphylaxis or severe allergic reactions, known allergies to any component of the investigational product, BCG intolerance
• Local and severe allergy (e.g. ulceration, systemic reactions) to PPD test
• Acute fever or fever (\>38.5˚C) in the last 7 days before registration
• Simultaneous administration of antituberculous agents and antibiotics that cannot be stopped until registration

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (16)

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum der Ruhr-Universität Bochum

Herne, 44625, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, 55131, Germany

Location

Klinikum Nürnberg - Universitätsklinik der Paracelsus Medizinischen Privatuniversität

Nuremberg, 90419, Germany

Location

Uniklinik Regensburg

Regensburg, 93053, Germany

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital-Basel

Basel, 4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital, Bern

Bern, 3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

Centre hospitalier universitaire vaudois CHUV

Lausanne, 1011, Switzerland

Location

Fondazione Oncologia Lago Maggiore

Locarno, 6600, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

• Rentsch CA, Thalmann GN, Lucca I, Kwiatkowski M, Wirth GJ, Strebel RT, Engeler D, Pedrazzini A, Huttenbrink C, Schultze-Seemann W, Torpai R, Bubendorf L, Wicki A, Roth B, Bosshard P, Puschel H, Boll DT, Hefermehl L, Roghmann F, Gierth M, Ribi K, Schafer S, Hayoz S. A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guerin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14. Eur Urol Oncol. 2022 Apr;5(2):195-202. doi: 10.1016/j.euo.2021.12.006. Epub 2022 Jan 7.

  PMID: 35012889 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

VPM1002 recombinant BCG vaccine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Cyrill Rentsch, MD, PhD

  University Hospital, Basel, Switzerland

  STUDY CHAIR

• Andreas Wicki, MD, PhD

  University Hospital, Basel, Switzerland

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: February 25, 2015
• Study Start: September 8, 2015
• Primary Completion: October 22, 2019
• Study Completion: March 7, 2023
• Last Updated: April 13, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6); CH (10)