Tetra-modality Bladder Preservation Strategies in Muscle-invasive Bladder Cancer: TURBT+ Chemo/Immunotherapy+ Radiation Therapy+ Maintenance Immunotherapy vs. W&W

NCT06686381 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: BIO-2024-0290
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the efficacy and safety of adding the immunotherapy Avelumab as a fourth component, alongside tumor removal, chemotherapy, and radiation, to increase the chance of preserving the bladder in the treatment of muscle-invasive bladder cancer.

Conditions

Muscle-invasive Bladder Cancer

Keywords

Muscle-invasive bladder cancer; Bladder preservation; Avelumab; Tetramodalities

Outcome Measures

Primary Outcomes (1)

• Efficacy of Avelumab in 2 non-comparative arms

  2 years proportion of MIBC bladder preserved participants in each tetra-modality arm.

  2 years

Secondary Outcomes (3)

• Response rate post-induction

  At week 17 (after 4 months of induction)

• Quality of life

  Every 3 weeks (up to 3 months), then every 4 months (up to 1 year)

• Safety

  During treatment (up to 90 days after end of treatment)

Study Arms (2)

Arm A (Maintenance Avelumab)

EXPERIMENTAL

Arm A: TURBT followed by induction Chemo/immunotherapy (DDMVAC (6 cycles) + Avelumab (6 cycles) or cisplatin/Gemzar (4 cycles) + Avelumab (6 cycles). A clinical evaluation is scheduled at 4 months post-day1 cycle 1 with CT scan/MRI for chest/abdomen/pelvis (CTCAP), Cystoscopy with Biopsy and urine cytology. Then complete or near complete responders will undergo 20 fractions of hypo-fractionated radiotherapy 55 grays followed by Avelumab every 2 weeks for 12-month maintenance phase.

Procedure: Maximum TURBT; Drug: Chemotherapy + Immunotherapy Induction; Radiation: Radiotherapy; Drug: Immunotherapy Maintenance

Arm B (W&W)

EXPERIMENTAL

Arm B: TURBT followed by induction Chemo/immunotherapy (DDMVAC (6 cycles) + Avelumab (6 cycles) or cisplatin/Gemzar (4 cycles) + Avelumab (6 cycles). A clinical evaluation is scheduled at 4 months post-day1 cycle 1 with CT scan/MRI for chest/abdomen/pelvis (CTCAP), Cystoscopy with Biopsy and urine cytology. Then complete or near complete responders will undergo 20 fractions of hypo-fractionated radiotherapy 55 grays followed by 1 year watch and wait.

Procedure: Maximum TURBT; Drug: Chemotherapy + Immunotherapy Induction; Radiation: Radiotherapy; Other: Watchful waiting with supportive care

Interventions

Maximum TURBT PROCEDURE

Total removal of the bladder tumor through TURBT

Arm A (Maintenance Avelumab); Arm B (W&W)

Chemotherapy + Immunotherapy Induction DRUG

Chemotherapy: DDMVAC (6 cycles) or Gemcitabine-Cisplatin (4 cycles) Immunotherapy: Avelumab (6 cycles)

Arm A (Maintenance Avelumab); Arm B (W&W)

Radiotherapy RADIATION

Hypofractionated radiotherapy: 20 fractions, 55 Grays

Arm A (Maintenance Avelumab); Arm B (W&W)

Immunotherapy Maintenance DRUG

Maintenance Avelumab every 2 weeks for 12 months

Arm A (Maintenance Avelumab)

Watchful waiting with supportive care OTHER

1 year watch and wait

Arm B (W&W)

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form (ICF) before any trial related procedures.
• Male or female participant with ≥ 18 years of age at time of consenting.
• Participant is able and willing to comply with the requirements of trial protocol.
• Pathologically (histologically or cytologically) and radiologically confirmed newly diagnosed MIBC (T2-T4 N0 M0) or recurrent previously NMIBC.
• Histologically confirmed transitional cell carcinoma.
• Participant with ECOG Performance Status (PS) ≤ 1 at screening visit.
• An estimated life expectancy of more than 6 months.
• At screening visit, Left Ventricular Ejection Fraction LVEF \>50% by echocardiography, for participants planned to receive DDMVAC.
• Participant must have adequate laboratory values at screening visit as follow:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
• Platelet count ≥ 100 × 10\^9/L
• Hemoglobin ≥ 9 g/dL (may have been transfused)
• Hepatic:
• Total bilirubin level ≤ 1.5 × ULN

You may not qualify if:

• Participant with non-muscle invasive bladder cancer or Metastatic disease (M1) and/or lymph node positive.
• Participant who underwent radical cystectomy or is planned for radical cystectomy.
• Histologically confirmed squamous cell carcinoma, micropapillary carcinoma, neuroendocrine carcinoma, adenocarcinoma, or mixed histology.
• Participant had received treatment for urothelial carcinoma, with any of the following anti-cancer therapies prior the first dose of trial treatment: systemic chemotherapy, targeted small molecule therapy, or radiation therapy.
• Participant had received prior treatment with any drug or antibody (anti-PD-1, anti-PD- L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody) targeting T-cell co-stimulation or checkpoint pathways.
• Participant who are not eligible to receive DDMVAC or Cisplatin-Gemzar.
• History of severe hypersensitivity to Avelumab or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI- CTCAE v5.0 Grade ≥ 3).
• Participant with hydronephrosis.
• Active infection requiring systemic therapy within 28 days before the first dose of trial treatment (e.g., urinary tract infection).
• History of testing positive for the human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening visit (positive Hepatitis B surface antigen (HBsAg) or HCV RNA if anti-HCV antibody screening test is positive).
• Participant currently using immunosuppressive medication, except for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection).
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent.
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

Sponsors & Collaborators

• American University of Beirut Medical Center: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

American University of Beirut

Beirut, Beyrouth, Lebanon

Location

Related Publications (1)

• Shamseddine A, Abbas N, Temraz S, Al Darazi M, Charafeddine M, Dagher K, Youssef B, Nasr R, Khauli R, El Hajj A, Bulbul M. Tetra-modality bladder preservation with avelumab for muscle-invasive urothelial cancer: a phase II trial (TRIUMPH-B01). Future Oncol. 2025 Dec;21(30):3873-3884. doi: 10.1080/14796694.2025.2549244. Epub 2025 Aug 25.

  PMID: 40851456 DERIVED

MeSH Terms

Interventions

Drug Therapy; Radiotherapy; Watchful Waiting; Palliative Care

Intervention Hierarchy (Ancestors)

Therapeutics; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Patient Care; Health Services; Health Care Facilities Workforce and Services

Central Study Contacts

Ali I. Shamseddine, MD, FRCP, ESCO

CONTACT

9311350000; as04@aub.edu.lb

Study Design

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

Model Details: This is a non-comparative, randomized trial, where each arm is independent from the other. Arm A will receive drug A in both the induction and maintenance phases, while Arm B will receive drug A during the induction phase and then follow a "watch and wait" approach.

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 13, 2024
• Study Start: April 15, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 15, 2028
• Last Updated: February 5, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)