Intravesical Recombinant BCG Followed by Perioperative Chemo-immunotherapy for Patients With MIBC

NCT04630730 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: SAKK 06/19
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 10

Brief Summary

Current treatment of localized muscle-invasive bladder cancer is still associated with high relapse and death rate as well as the need for complete bladder resection or irradiation. The primary objective of this trial is to increase the rate of pathologic complete remission (pCR) at the time of radical cystectomy by the combination of local bladder instillation with Bacillus Calmette Guérin (BCG) in combination with systemic immunotherapy with atezolizumab and standard chemotherapy with cisplatin/gemcitabine. The trial tests the hypothesis whether BCG can enhance systemic and local immune response and thereby increase pCR rate and consequently also event-free survival. Improving pCR rate would be a next step to the ultimate goal of omitting radical surgery or extensive local radiotherapy to the bladder for these patients.

Conditions

Bladder Cancer

Keywords

muscle-invasive bladder cancer; MIBC; intravesical BCG; Bacillus Calmette Guérin; VPM1002BC; atezolizumab; Cisplatin; Gemcitabine; neoadjuvant; adjuvant

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission (pCR)

  The primary endpoint of the trial is pCR after neoadjuvant treatment defined as ypT0ypN0 and no evidence of non-muscle invasive bladder cancer (low grade, high grade or CIS). The primary analysis will be based on the results from central pathology review.

  At the date of tumor assessment after surgery, estimated at approximately 20 to 24 weeks after treatment start

Secondary Outcomes (10)

• Event-free survival (EFS)

  From the date of treatment start until the date of progressive disease, recurrence of locoregional disease, appearance of metastases or death, whichever occurs first, assessed up to 5 years after surgery

• Recurrence-free survival (RFS) after R0 resection

  From the date of surgery until the date recurrence of locoregional disease, appearance of metastases or death, whichever occurs first, assessed up to 5 years after surgery

• Overall survival (OS)

  From the date of treatment start until the date of death, assessed up to 5 years after surgery

• Quality of resection: Complete resection

  At the date of tumor assessment after surgery, estimated at approximately 20 to 24 weeks after treatment start

• Quality of resection: Completeness of the lymphadenectomy and surgery

  At the date of tumor assessment after surgery, estimated at approximately 20 to 24 weeks after treatment start

Study Arms (1)

Recombinant intravesical BCG

EXPERIMENTAL

The Intravesical recombinant BCG (Bacillus Calmette-Guérin - VPM1002BC) is used as an immuno-stimulating agent. The patient will receive 3 weekly BCG instillations as induction treatment. 4 cycles of atezolizumab, a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1 inhibitor) will be administered in combination with the standard neoadjuvant chemotherapy cisplatin/gemcitabine. After surgery atezolizumab will be administered in the adjuvant setting for 13 cycles.

Drug: Recombinant intravesical BCG (Bacillus Calmette-Guérin VPM1002BC); Drug: Atezolizumab; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Recombinant intravesical BCG (Bacillus Calmette-Guérin VPM1002BC) DRUG

1 dose of VPM1002BC, live, 1-19.2 x 108 colony forming units (CFU) on day 1, 8 (+/- 1 day) and 15 (+/- 1 day)

Also known as: VPM1002BC

Recombinant intravesical BCG

Atezolizumab DRUG

Neoadjuvant immunotherapy with atezolizumab, 4 cycles 1200 mg fixed dose iv infusion on d1 q3w starting 4-16 weeks after date of surgery

Also known as: Tecentriq™

Recombinant intravesical BCG

Cisplatin DRUG

Neoadjuvant chemotherapy with cisplatin: 4 cycles 70mg/m2 iv infusion on d1 q3w (starting on d22)

Also known as: Platinol®

Recombinant intravesical BCG

Gemcitabine DRUG

Neoadjuvant chemotherapy with gemcitabine: 4 cycles 1000 mg/m2 iv infusion on d1 and d8 q3w (starting on d22)

Also known as: Gemzar ®

Recombinant intravesical BCG

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
• Histologically proven urothelial cell carcinoma of the bladder (cT2, cT3 or cT4a and ≤ cN1 (defined as a solitary lymph node ≤ 2 cm in the greatest dimension) and cM0) and be considered suitable for curative multimodality treatment including radical cystectomy by a multidisciplinary tumor board
• All histological subtypes eligible with the exception of small cell component
• Age ≥ 18 years
• WHO performance status 0-1
• Hematological function: hemoglobin ≥ 90 g/L, neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
• Hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST ≤ 2.5 x ULN and ALT ≤ 2.5 x ULN, AP ≤ 2.5 x ULN
• Renal function: estimated glomerular filtration rate (eGFR) \> 50 mL/min/1.73m², according to CKD-EPI formula
• Women of childbearing potential must use effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and until 5 months after the last dose of investigational drug
• Men agree not to donate sperm or to father a child during trial treatment and until 5 months after the last dose of investigational drug (www.swissmedicinfo.ch).

You may not qualify if:

• Any pathological evidence of small-cell carcinoma component
• Presence of any distant metastasis
• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years after registration, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer or low risk localized prostate cancer (T1-T2a, Gleason \<7, PSA \<10ng/ml)
• Residual urinary bladder volume after micturition \> 150ml (measured by ultrasound of bladder or inserted catheter)
• Prior treatment for bladder cancer including BCG instillations. Single dose intravesical chemotherapy instillation after TURB is allowed
• Bladder surgery or traumatic catheterization or TURB within 14 days prior to the expected start of BCG trial treatment
• Uncontrollable urinary tract infection, macroscopic haematuria, suspicion of bladder perforation, urethral strictures (if interfering with trial procedures)
• Any conditions preventing the patient from keeping BCG instillation in the bladder for at least 1 hour; anticholinergics are allowed to achieve this criterion
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including atezolizumab
• Concomitant or prior use of immunosuppressive medication within 28 days before registration, with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids which must not exceed 10 mg/day of prednisone (or a dose equivalent corticosteroid) and the premedication for chemotherapy
• Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 28 days prior to registration
• Major surgical procedure within 28 days prior to registration
• Preexisting peripheral neuropathy (\> grade 1)
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (10)

Klinik Hirslanden - Onkozentrum Hirslanden

Zurich, Canton of Zurich, 8032, 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

Lindenhofspital

Bern, 3012, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Hôpitaux Universitaires Genève HUG

Geneva, 1211, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Petrausch U, Spahn M, Schneider M, Hayoz S, Rentsch CA, Rothschild S, Omlin A, Cathomas R. Novel sequential treatment strategy for patients with muscle-invasive bladder cancer (MIBC): intravesical recombinant BCG, followed by neoadjuvant chemoimmunotherapy, radical cystectomy plus pelvic lymphadenectomy and adjuvant immunotherapy - protocol of a multicentre, single arm phase 2 trial (SAKK 06/19). BMJ Open. 2023 Jun 7;13(6):e067634. doi: 10.1136/bmjopen-2022-067634.

  PMID: 37286312 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

atezolizumab; Cisplatin; Gemcitabine

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Richard Cathomas, MD

  Kantonsspital Graubünden, Chur

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective single-arm open-label multicenter phase II trial

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 16, 2020
• Study Start: June 24, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2030
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

CH (10)