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Immunogenic Cell Death as a Novel Mechanism of Mitomycin C Activity in Bladder Cancer (ICH-MIM-01)

4. juli 2020 oppdatert av: Michele Tedeschi, Istituto Clinico Humanitas
The principal objective of this study consists in the assessment of Immunogenic Cell Death (ICD) induction in neoplastic tissues derived from bladder cancer patients treated ex vivo with Mitomycin C (MMC). The evaluation is performed using cellular and molecular analyses of treated versus untreated samples derived from the same patient

Studieoversikt

Status

Ukjent

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Urothelial or transitional cell carcinoma of the bladder is the fourth most common cancer in males worldwide, with about 60-80% of newly diagnosed patients having non-muscle-invasive bladder cancer (NMIBC). NMIBC management consist in transurethral resection of bladder tumor (TURBT) followed by adjuvant intravesical treatment with the chemotherapeutic agent Mitomycin C (MMC) or the immunotherapy bacillus Calmette-Guérin. These therapies result in low progression rates, but are not efficacious in all patients, leading to high tumor recurrence. Immunogenic cell death (ICD) may be one of the mechanisms of action of MMC intravesical therapy in bladder cancer.

The primary objective of the study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues. As secondary targets we aim to:

  1. identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature'),
  2. asses the genetic and environmental factors- urinary microbiome composition- responsible for MMC treatment efficacy,
  3. evaluate whether ICD induction correlates with clinical staging and response (clinical endpoints for MMC-treated patients are recurrence at three month and one year after enrollment).

Studietype

Observasjonsmessig

Registrering (Forventet)

110

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Italia
    • Milan
      • Rozzano, Milan, Italia, 20089
        • Rekruttering
        • Humanitas reseach hospital (ICH)

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

40 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

80 patients with carcinoma of the bladder; divided in 20 patients Ta (low grade), 20 patients Ta/T1 (high grade) and 20 patients T2. Only for liquid samples collection we will include 20 CIS (carcinoma in situ) patients.

30 age and sex-matched subjects not suffering from carcinoma of the bladder, already hospitalized in ICH; we expect to enroll 24 males and 6 females of which 10 of 40- 60 years old, 10 of 60-70 years old, 10 of >70 years old.

Beskrivelse

Inclusion Criteria:

- Male and females, > 40 years old

For bladder cancer patients:

- bladder cancer patients- patinets with first tumor occurrence or patient with a recurrence after more than 2 years from the removal of the prior malignancy

Exclusion Criteria:

  • Treated with immunomodulatory agents at time of enrollment or in the two months before enrollment
  • Treated with antibiotics at time of enrollment or during the month before enrollment
  • Positive history of sexually transmitted diseases
  • Urinary infection ongoing or recent (during the three months before enrollment)
  • Suffering from chronic intestinal inflammation

ONLY for controls:

  • Treated with immunomodulatory agents at time of enrollment or in the two months before enrollment
  • Treated with antibiotics at time of enrollment or during the month before enrollment
  • Positive history of sexually transmitted diseases
  • Urinary infection ongoing or recent (during the three months before enrollment)
  • Suffering from chronic intestinal inflammation

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Kohorter og intervensjoner

Gruppe / Kohort
Intervensjon / Behandling
Bladder cancer patients
80 patients with carcinoma of the bladder; divided in 20 patients Ta (low grade), 20 patients Ta/T1 (high grade) and 20 patients T2. Only for liquid samples collection we will include 20 CIS (carcinoma in situ) patients
Annen: This is an observational study that does not concern a direct intervention on patients and control subjects and does not interfere with the clinical management of patients.

urine collection: DNA is isolated from urine samples (catheterized, washout, midstream) and the 16S rRNA gene is sequenced.

Specimen collection: Specimens collected during TURBT are selected by a pathologist and trasferred to the laboratory. The tissues are treated ex vivo with MMC.
Controls- Healthy subjects
30 age and sex-matched subjects not suffering from carcinoma of the bladder, already hospitalized in ICH; we expect to enroll 24 males and 6 females of which 10 of 40- 60 years old, 10 of 60-70 years old, 10 of >70 years old.
Annen: This is an observational study that does not concern a direct intervention on patients and control subjects and does not interfere with the clinical management of patients.

urine collection: DNA is isolated from urine samples (catheterized, washout, midstream) and the 16S rRNA gene is sequenced.

Specimen collection: Specimens collected during TURBT are selected by a pathologist and trasferred to the laboratory. The tissues are treated ex vivo with MMC.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
MMC-induced ICD
Tidsramme: 3 years
The main aim of this study is to evaluate whether MMC is able to trigger ICD in patient-derived neoplastic tissues.
3 years

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
ICD signature analyzed by RNAseq analysis
Tidsramme: 3 years
Identify an expression profile that is common to all tumors that undergo ICD upon MMC treatment ('ICD signature')
3 years
Microbiota study
Tidsramme: 3 years
Verify the existance of urinary microbiome using catheterized urines and identify changes in urinary microbiome composition correlating with bldder cancer, MMC efficacy and staging/progression of the disease
3 years

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Istituto Clinico Humanitas

Publikasjoner og nyttige lenker

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Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

27. juni 2018

Primær fullføring (Forventet)

1. september 2020

Studiet fullført (Forventet)

30. september 2020

Datoer for studieregistrering

Først innsendt

3. februar 2020

Først innsendt som oppfylte QC-kriteriene

3. februar 2020

Først lagt ut (Faktiske)

5. februar 2020

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

7. juli 2020

Siste oppdatering sendt inn som oppfylte QC-kriteriene

4. juli 2020

Sist bekreftet

1. juli 2020

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 2041

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

Research outcome

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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