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Muscle-invasive Bladder CancerPhase 2NCT06686381

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

A Phase 2 study testing Maximum TURBT, Chemotherapy + Immunotherapy Induction and Radiotherapy in people with Muscle-invasive Bladder Cancer, run by American University of Beirut Medical Center at 1 site in Lebanon.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Muscle-invasive Bladder Cancer
What is being tested?
Maximum TURBT, Chemotherapy + Immunotherapy Induction and Radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteLebanon
Study dates
11 Jun 2025to 15 Aug 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • AST ≤ 2.5 × ULN
  • ALT ≤ 2.5 × ULN
  • Renal:
  • Estimated creatinine clearance > 50 mL/min according to the Cockcroft-Gault formula
  • Serum urea ≤ 1.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN.
  • Female participant of childbearing potential must have a negative serum pregnancy test at screening.
  • For female participant of childbearing potential: use one of the following highly effective contraception methods throughout the trial and for 30 days after the last Avelumab treatment administration.
  • combined (estrogen and progesterone) hormonal contraception associated with inhibition of ovulation: either oral, intravaginal or transdermal
  • progesterone-only hormonal contraception associated with inhibition of ovulation: either oral, injectable or implantable
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system (IUS)
  • bilateral tubal occlusion
  • vasectomised partner (provided that partner is the sole sexual partner of the female trial participant and that the vasectomised partner has received medical assessment of the surgical success)
  • sexual abstinence

Who cannot join

  • 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.
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  • 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).
  • Active autoimmune diseases that might deteriorate upon receiving an immune- stimulatory agent. Conditions such as vitiligo, psoriasis, diabetes type I, or hypo - or hyper-thyroid diseases not requiring immunosuppressive treatment are eligible.
  • Participant has any of the following medical conditions: Addison's disease, thyroiditis/Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, and Grave's disease.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent form.
  • Hepatic insufficiency manifesting as clinical jaundice, hepatic encephalopathy, and/or variceal bleed within 60 days prior to screening.
  • Clinically significant, active cardiovascular disease, such as:
  • Transmural myocardial infarction within 6 months of enrollment
  • Unstable angina
  • Congestive heart failure (New York Heart Association Classification Grade II or greater)
  • Serious cardiac arrhythmia requiring medical treatment
  • Cerebral vascular accident/ stroke within 6 months of enrollment.
  • End-stage renal disease requiring dialysis.
  • Participant has severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Treatment with an investigational agent within 28 days before the first dose of trial treatment.
  • Participation in another clinical trial.
  • Participants who are taking prohibited medication.
  • Pregnant or breastfeeding women or who are planned to get pregnant or breastfeed during the trial.
  • Vaccination within 4 weeks of the first dose of Avelumab is prohibited except for administration of inactivated vaccines.
  • Persisting toxicity related to prior therapy with Grade > 1 (NCI-CTCAE v 5.0); with the exception of: alopecia, sensory neuropathy Grade ≤ 2, or other toxicity with Grade ≤ 2 not constituting a safety risk based on investigator's judgment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ali I. Shamseddine, MD, FRCP, ESCO contact

9311350000 ext. 5390

as04@aub.edu.lb

Lebanon1 site, 1 recruiting

  • American University of Beirut

    Beirut, Beirut

    Monita H Darazi, Master in science, 961-3-166385, ma99@aub.edu.lb

    Kristel K Dagher, MBA, 961-3-724383, kd17@aub.edu.lb

    Recruiting

Other trials in Lebanon

About this study

Official title: A Phase II, Randomized, Non-comparative Double Arm, Open-label, 2-stage, Multicenter Study to Evaluate the Efficacy and Safety of 2 Tetra-modality Bladder Preservation Strategies in Muscle-invasive Bladder Cancer With Maximum TURBT Followed by Induction Platinum-based Chemotherapy/Avelumab Followed by Radiation Therapy Then Maintenance Avelumab or Watch and Wait Approach

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.

Read the detailed description

Muscle-invasive bladder cancer (MIBC) is an aggressive form of bladder cancer, with a 5-year survival rate of about 40%.

The standard treatment for MIBC is induction platinum-based chemotherapy followed by radical cystectomy. Recently bladder preservation strategies have emerged as an alternative to radical cystectomy, particularly useful for patients who are unfit for surgery or would rather opt for non-surgical approaches. Knowing the high risks related to surgery and its significant complications, the investigators propose to implement 2 tetra-modalities treatment strategies to increase the chance of preserving the bladder and decrease the need of salvage cystectomy.

The purpose of this study is to assess the efficacy and safety of 2 bladder-preservation treatments plans called tetra-modalities:

First plan:

  • maximium TURBT
  • chemo-immunotherapy as induction phase (Avelumab added to chemotherapy)
  • radiation therapy
  • maintenance phase with Avelumab

Second plan:

  • Maximum TURBT
  • chemo-immunotherapy as induction phase (Avelumab added to chemotherapy)
  • radiation therapy
  • Watch and wait

Both tetra-modalities duration will last maximum of 2 years from patient inclusion.

These treatment plans are based on the synergistic action between immunotherapy, chemotherapy, and radiotherapy. The use of Avelumab in the maintenance group is supported by its proven success in treating advanced cancer and various studies looking at immunotherapy as a way to avoid or delay bladder removal.

Being tested
Maximum TURBT, Chemotherapy + Immunotherapy Induction, Radiotherapy, Immunotherapy Maintenance, Watchful waiting with supportive care
Keywords
Muscle-invasive bladder cancer, Bladder preservation, Avelumab, Tetramodalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Maximum TURBTProcedure or surgery

    Total removal of the bladder tumor through TURBT

  • Chemotherapy + Immunotherapy InductionDrug

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

  • RadiotherapyRadiation

    Hypofractionated radiotherapy: 20 fractions, 55 Grays

  • Immunotherapy MaintenanceDrug

    Maintenance Avelumab every 2 weeks for 12 months

  • Watchful waiting with supportive careOther

    1 year watch and wait

Study groups in NCT06686381
Study groupRoleWhat they receive
Arm A (Maintenance Avelumab)ExperimentalArm 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.
Receives: Procedure: Maximum TURBT; Drug: Chemotherapy + Immunotherapy Induction; Radiation: Radiotherapy; Drug: Immunotherapy Maintenance
Arm B (W&W)ExperimentalArm 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.
Receives: Procedure: Maximum TURBT; Drug: Chemotherapy + Immunotherapy Induction; Radiation: Radiotherapy; Other: Watchful waiting with supportive care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. to assess the proportion of patients who are radical cystectomy free at 2 years in the 2 non-comparative arms

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

    Measured: 2 years

Secondary outcomes (3)

  1. Response rate post-induction

    Response rate of participants in each arm following induction chemo/immunotherapy

    Measured: At week 17 (after 4 months of induction)

  2. Quality of life

    Effect of each tetra-modality arm on the quality of life of participants using the Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) questionnaire; FACT-Bl total score range: 0-156 (higher scores mean worse quality of life)

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

  3. Safety

    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2024
  2. Study start11 Jun 2025
  3. Primary completionAug 2028 (estimated)
  4. Study completion15 Aug 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06686381
Sponsor's protocol ID
BIO-2024-0290
Status last verified
Oct 2026
First submitted
5 Nov 2024
Last updated
29 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40851456

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Maximum TURBT, Chemotherapy + Immunotherapy Induction and Radiotherapy in people with Muscle-invasive Bladder Cancer, run by American University of Beirut Medical Center at 1 site in Lebanon.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Lebanon. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ali I. Shamseddine, MD, FRCP, ESCO (9311350000 ext. 5390, as04@aub.edu.lb), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

to assess the proportion of patients who are radical cystectomy free at 2 years in the 2 non-comparative arms (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06686381, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.

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Clinical Trial NCT06686381 | AzTrials