Is Prolonged Systemic Immunotherapy Necessary After Achieving Tumor-free Status in Patients With Extensive Transurethrally Unresectable Very-high-risk NMIBC?
Randomized Trial of Active Surveillance Versus Continued Systemic Immunotherapy After Achieving Tumor-Free Status in Extensive Transurethrally Unresectable Very-High-Risk NMIBC
Patients with extensive transurethrally unresectable very-high-risk non-muscle-invasive bladder cancer (NMIBC) may achieve a tumor-free status after systemic immunotherapy-based bladder-sparing treatment combined with transurethral resection of bladder tumor (TURBT). However, the optimal duration of systemic immunotherapy after achieving a tumor-free status remains uncertain. Prolonged treatment may increase toxicity, treatment burden, and cost, while some patients may maintain durable disease control without continued therapy.
This randomized study aims to evaluate whether active surveillance after achieving tumor-free status is a feasible alternative to continued systemic immunotherapy in patients with extensive transurethrally unresectable very-high-risk NMIBC.
Patients will initially receive systemic immunotherapy-based treatment followed by disease evaluation using cystoscopy with biopsy and/or TURBT, urine cytology, urinary tumor DNA (utDNA), and imaging assessments. Patients who achieve tumor-free status after treatment and complete resection of visible disease will be randomized to either active surveillance or continued systemic immunotherapy.
The study will evaluate recurrence outcomes, bladder preservation, progression, safety, and patient management strategies following achievement of tumor-free status. The trial also aims to explore the role of urinary tumor DNA in identifying patients who may safely undergo treatment de-escalation and active surveillance.
Tutkimuksen yleiskatsaus
Tila
Tila
Ehdot
Ehdot
Interventio / Hoito
Interventio / Hoito
Opintotyyppi
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Ilmoittautuminen
Vaihe
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskeluyhteys
Opiskeluyhteys
- Nimi: Hailong Hu, MD
- Puhelinnumero: +8619801518556
- Sähköposti: huhailong@tmu.edu.cn
Tutki yhteystietojen varmuuskopiointi
- Nimi: Yunkai Qie, MD
- Sähköposti: qieyunkai@tmu.edu.cn
Opiskelupaikat
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-
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Tianjin, Kiina
- General Hospital of Tianjin Medical University
-
Ottaa yhteyttä:
- Liang Wang
- Puhelinnumero: +8615620530409
- Sähköposti: wjlmnwk@163.com
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Tianjin, Kiina, 300000
- The Second Hospital of Tianjin Medical University
-
Ottaa yhteyttä:
- Hailong Hu
- Puhelinnumero: +8619801518556
- Sähköposti: huhailong@tmu.edu.cn
-
Tianjin, Kiina
- Tianjin Hospital
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Ottaa yhteyttä:
- Guangbin Zhu
- Puhelinnumero: +8613903124399
- Sähköposti: zgb2016@163.com
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Xingtai, Kiina
- Xingtai People's Hospital
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Ottaa yhteyttä:
- Junli Wei
- Puhelinnumero: +8617299180245
- Sähköposti: wjluro@163.com
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Kuvaus
Inclusion Criteria
- Has histologically confirmed very-high-risk non-muscle-invasive urothelial carcinoma of the bladder.
- Has transurethrally unresectable bladder tumor, defined as visually incomplete TURBT and/or extensive high-volume disease considered unsuitable for complete and oncologically adequate transurethral resection.
- Has undergone cystoscopy and TURBT evaluation before study enrollment.
- Has received systemic PD-1/PD-L1 inhibitor-based bladder-sparing therapy before randomization.
Has achieved tumor-free status before randomization, defined as:
- No visible bladder tumor on cystoscopy;
- Negative bladder biopsy and/or TURBT pathology;
- Negative urine cytology;
- Negative urinary tumor DNA (utDNA);
- No radiographic evidence of progression or metastasis.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Has adequate organ function.
- Has provided written informed consent.
Cohort A Only
- Achieved tumor-free status at the initial response evaluation after induction systemic therapy.
- Maintained tumor-free status after additional systemic therapy before randomization.
Cohort B Only
- Did not achieve tumor-free status at the initial response evaluation because of residual non-muscle-invasive disease.
- Subsequently underwent complete TURBT/resection of residual disease followed by additional systemic therapy.
- Achieved tumor-free status at the second response evaluation before randomization.
Exclusion Criteria
- Has muscle-invasive bladder cancer (≥T2), locally advanced unresectable disease, nodal disease, or distant metastasis.
- Has concurrent upper tract urothelial carcinoma.
- Has persistent visible tumor, positive bladder pathology, positive urine cytology, or positive utDNA before randomization.
- Has received prior systemic immunotherapy for metastatic urothelial carcinoma.
- Has active autoimmune disease requiring systemic treatment.
- Is receiving systemic immunosuppressive therapy.
- Has uncontrolled infection requiring systemic therapy.
- Has another active malignancy requiring systemic treatment.
- Has known active hepatitis B, hepatitis C, human immunodeficiency virus infection, or active tuberculosis.
- Has pregnancy or breastfeeding.
- Has any medical or psychiatric condition that, in the investigator's judgment, would interfere with study participation or interpretation of results.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseiden lukumäärä
Aseet ja interventiot
Osallistujaryhmä / ArmOsallistujaryhmä / Arm |
Interventio / HoitoInterventio / Hoito |
|---|---|
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Kokeellinen: Arm A-1 (Cohort A Active Surveillance)
Patients in Cohort A who achieve early tumor-free status after initial systemic immunotherapy-based treatment will undergo active surveillance with protocol-defined cystoscopy, urine cytology, urinary tumor DNA testing, biopsy as clinically indicated, and imaging assessments.
|
Patients undergo protocol-defined surveillance after achieving tumor-free status, including cystoscopy, biopsy as clinically indicated, urine cytology, urinary tumor DNA testing, and imaging assessments, without continued systemic PD-1/PD-L1 inhibitor therapy unless disease recurrence or progression occurs.
|
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Active Comparator: Arm A-2 (Cohort A Continued Systemic Immunotherapy)
Patients in Cohort A who achieve early tumor-free status after initial systemic immunotherapy-based treatment will continue systemic immunotherapy for a protocol-defined duration with ongoing disease surveillance.
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Patients continue protocol-defined systemic PD-1/PD-L1 inhibitor therapy after achieving tumor-free status for up to approximately 1 year, with ongoing surveillance including cystoscopy, urine cytology, urinary tumor DNA testing, and imaging assessments.
|
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Kokeellinen: Arm B-1 (Cohort B Active Surveillance)
Patients in Cohort B who do not achieve tumor-free status at initial evaluation but subsequently achieve tumor-free status after complete TURBT/resection and additional systemic immunotherapy will undergo active surveillance with protocol-defined surveillance assessments.
|
Patients undergo protocol-defined surveillance after achieving tumor-free status, including cystoscopy, biopsy as clinically indicated, urine cytology, urinary tumor DNA testing, and imaging assessments, without continued systemic PD-1/PD-L1 inhibitor therapy unless disease recurrence or progression occurs.
|
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Active Comparator: Arm B-2 (Cohort B Continued Systemic Immunotherapy)
Patients in Cohort B who subsequently achieve tumor-free status after complete TURBT/resection and additional systemic immunotherapy will continue systemic immunotherapy for a protocol-defined duration with ongoing disease surveillance.
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Patients continue protocol-defined systemic PD-1/PD-L1 inhibitor therapy after achieving tumor-free status for up to approximately 1 year, with ongoing surveillance including cystoscopy, urine cytology, urinary tumor DNA testing, and imaging assessments.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Bladder-intact event-free survival (BI-EFS)
Aikaikkuna: Up to 2 years from randomization
|
Time from randomization to the first occurrence of high-risk NMIBC recurrence, progression to muscle-invasive bladder cancer, distant metastasis, radical cystectomy, or death from any cause.
|
Up to 2 years from randomization
|
Toissijaiset tulostoimenpiteet
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Recurrence-free survival (RFS)
Aikaikkuna: Up to 2 years from randomization
|
Time from randomization to the first documented recurrence of bladder cancer or death from any cause.
|
Up to 2 years from randomization
|
|
Progression-free survival (PFS)
Aikaikkuna: Up to 2 years from randomization
|
Time from randomization to progression to muscle-invasive, locally advanced, or metastatic bladder cancer, or death from any cause.
|
Up to 2 years from randomization
|
|
Radical cystectomy-free survival (RCFS)
Aikaikkuna: Up to 2 years from randomization
|
Time from randomization to radical cystectomy or death from any cause.
|
Up to 2 years from randomization
|
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Overall survival (OS)
Aikaikkuna: Up to 2 years from randomization
|
Time from randomization to death from any cause.
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Up to 2 years from randomization
|
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Incidence of treatment-related adverse events
Aikaikkuna: Up to 2 years from randomization
|
Proportion of patients experiencing treatment-related adverse events, graded according to CTCAE.
|
Up to 2 years from randomization
|
Muut tulostoimenpiteet
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Recurrence-Free Survival According to Urinary Tumor DNA Status
Aikaikkuna: Up to 2 years from randomization
|
Recurrence-free survival will be evaluated according to urinary tumor DNA status after achieving tumor-free status.
Urinary tumor DNA status will be assessed using a urine-based tumor DNA assay and categorized as positive or negative.
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Up to 2 years from randomization
|
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utDNA conversion during surveillance
Aikaikkuna: Up to 2 years from initial systemic administration
|
Proportion of patients with conversion from urinary tumor DNA negative to positive during follow-up.
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Up to 2 years from initial systemic administration
|
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Bladder-Intact Event-Free Survival According to Response Cohort in the Active Surveillance Arm
Aikaikkuna: Up to 2 years from randomization
|
Bladder-intact event-free survival will be compared between participants assigned to active surveillance in Cohort A and Cohort B.
|
Up to 2 years from randomization
|
|
Recurrence-Free Survival According to Response Cohort in the Active Surveillance Arm
Aikaikkuna: Up to 2 years from randomization
|
Recurrence-free survival will be compared between participants assigned to active surveillance in Cohort A and Cohort B.
|
Up to 2 years from randomization
|
|
Bladder-Intact Event-Free Survival According to Response Cohort in the Continued Systemic Immunotherapy Arm
Aikaikkuna: Up to 2 years from randomization
|
Bladder-intact event-free survival will be compared between participants assigned to continued systemic immunotherapy in Cohort A and Cohort B.
|
Up to 2 years from randomization
|
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Recurrence-Free Survival According to Response Cohort in the Continued Systemic Immunotherapy Arm
Aikaikkuna: Up to 2 years from randomization
|
Recurrence-free survival will be compared between participants assigned to continued systemic immunotherapy in Cohort A and Cohort B.
|
Up to 2 years from randomization
|
Yhteistyökumppanit ja tutkijat
Sponsori
Sponsori
Tutkijat
Tutkijat
- Päätutkija: Hailong Hu, MD, Department of Urology, The Second Hospital of Tianjin Medical University
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Opiskelun aloitus
Ensisijainen valmistuminen (Arvioitu)
Ensisijainen valmistuminen
Opintojen valmistuminen (Arvioitu)
Opintojen valmistuminen
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Ensimmäinen Lähetetty
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin päivitys julkaistu
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Viimeksi vahvistettu
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