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Enfortumab Vedotin + Pembrolizumab Induction to Spare the Bladder in MIBC

ConditionUrothelial Bladder Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Netherlands Cancer Institute

About this trial

This is a Phase 2 clinical intervention trial to assess efficacy of induction EVP to spare the bladder in stage T2-4aN0-1 urothelial bladder cancer (UBC), using a response-adapted approach

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants who are at least 18 years of age on the day of signing informed consent.

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

Patients with histologically confirmed cT2-4aN0-1M0 urothelial bladder cancer, seeking an alternative to radical cystectomy and/or patients who are medically unfit for surgery.

no pure (>90%) squamous

Disqualifiers

Previous pelvic irradiation

Upper tract urothelial cancer

Extensive carcinoma in situ (CIS) of the bladder

Bilateral hydronephrosis

Trial design

Design model

Parallel

Treatments tested in this trial

  • Enfortumab Vedotin

    Drug

    Induction: 4 cycles (d1,8; 1.25 mg/kg)

  • Pembrolizumab

    Drug

    Induction: 4 cycles 200mg and after cCR 400 mg q6 weeks. Total 1 year from start of therapy

  • Radiation

    Radiation

    The preference will be a four-week schedule, in which 55 Gy radiotherapy will be administered using intensity modulated radiation therapy (IMRT)

  • Chemoradiation

    Other intervention

    by local protocol; by local protocol; Mitomycin C/fluoropyrimidines in the Netherlands) * No disease outside the bladder (e.g. involvement of ureter, prostatic urethra or (suspected) lymph node metastases) * No bilateral hydronephrosis * No multifocal CIS * Adequate bladder function: Post-micturition residual volume of \< 200 cc, International Prostate Symptom Score (IPSS) \< 15 points; revised urinary incontinence scale \< 8 points; no daily or continuous catheter use.

  • Cystectomy

    Procedure/Surgery

    Surgical removal of the bladder

Treatment groups

56 Participants
are divided into 4 treatment groups
Group A: After induction therapy and cCR: maintenance pembrolizumab onlyExperimental treatment 2 interventions
Group B: After induction therapy and cCR: consolidative radiotherapy, followed by maintenance pembrolizumab.Experimental treatment 3 interventions
Group C: By residual disease may still receive bladder-sparing treatmentOther 3 interventions
Group D: By residual disease cannot receive bladder-sparing treatmentOther 3 interventions

Trial outcomes

Primary outcomes

1

Estimated 2-year bladder-intact event-free survival (BI-EFS) for the intention-to-treat population, measured from day 1 of treatment until the moment of analysis

Bladder-intact event-free survival (BI-EFS). The primary analysis will be performed after the last participant has completed at least 15 months of follow-up from the first dose of study treatment or when 21 BI-EFS events have been observed, whichever occurs first.

Time frame
From the first dose of study treatment up to 2 years of follow-up

Secondary outcomes

1

Feasibility of observation vs consolidative RT (followed by maintenance pembrolizumab) in cCR patients after induction EVP: rate of cystectomy and/or muscle-invasive and non-muscle invasive recurrence per arm.

Rate of cystectomy and/or muscle-invasive and non-muscle invasive recurrence per cCR treatment arm

Time frame
From cCR assesment until cystectomy and/or muscle-invasive or non-muscle-invasive recurrence, assessed up to 66 months.
2

Overall survival (OS)

OS is defined as the time between the date of enrollment and the date of death. OS will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported.

Time frame
From the date of enrollment until death from any cause, assessed up to 66 months.
3

Progression-free survival (PFS)

PFS is defined as time from start of therapy until an event or death by any cause

Time frame
From the first dose of study treatment until the first documented disease progression or death from any cause, assessed up to 66 months.
4

Metastasis-free survival (MFS)

• Time from start of therapy until occurrence of nodal or distant metastases, or progression of nodal metastases present at baseline by RECIST1.1 measurement

Time frame
From the first dose of study treatment until the first documented disease progression or death from any cause, assessed up to 66 months.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

The Netherlands Cancer Institute

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Astellas Pharma Inc

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: