Predicting Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer

NCT06325423 | Not Yet Recruiting FDA Drug

• 1 other identifier: response to NAC in MIBC
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Bladder cancer (BC) is the 10th most commonly diagnosed cancer worldwide and the second most common cancer among Egyptian males. The mainstay of treatment of muscle-invasive BC( MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or bladder preservation(BP) using maximal transurethral resection of the bladder tumor followed by chemoradiation. The rationale to use NAC before RC or BP is to eradicate micro-metastasis and to downstage the primary tumor. The 5-year cancer-specific survival for responders to NAC is 90%, in contrast to 30-40% for those not obtaining an objective response. Drawbacks of NAC are disappointing delay of surgery in non-responders and the potential toxicity. So, predictors of response to NAC are necessary to identify patients who may achieve pathologic complete response and will benefit from BP, and the others who may not respond to NAC and spare them NAC toxicity and RC delay. Tumor microenvironment (TME), including neutrophil extracellular traps (NETs), and CD8+ T lymphocytes is a promising predictor of response to NAC in MIBC. NETs are reticulated DNA structures decorated with various protein substances (e.g., histones, myeloperoxidase, neutrophil elastase).NETs are involved in tumor growth, metastasis, and treatment resistance. Moreover, NETs can inhibit T cell responses, thereby promoting tumor growth. On the other hand, immune cells that are present in the TME play a major role in slowing down tumor progression. CD8+T lymphocytes play a central role in immune-mediated control of cancer . Also, they have been found to be a prognostic tool for advanced BC.

Conditions

Muscle-Invasive Bladder Carcinoma

Keywords

MIBC

Outcome Measures

Primary Outcomes (2)

• Evaluation of the expression of NETs and CD8 in paraffin-embedded TUR biopsies

  evaluation of the density of Citrullinated Histone H3 as a hallmark of NETs and the density of CD8 in the baseline FFPE TUR specimens

  6 months

• - Response to platinum-based chemotherapy in localized MIBC in relation to: NETs expression, CD8 expression, NET/CD8 ratio and baseline clinicopathological features

  Correlation between NETs expression, CD8 expression, NETs/CD8 ratio and the baseline clinicopathological features of MIBC and the response to neoadjuvant chemotherapy

  6 months

Secondary Outcomes (1)

• Local recurrence-free survival (RFS)

  2 years

Study Arms (1)

MIBC patients who received NAC

Patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy before radical cystectomy or bladder preservation

Combination Product: neoadjuvant chemotherapy

Interventions

neoadjuvant chemotherapy COMBINATION_PRODUCT

platinum-based chemotherapy before radical cystectomy or bladder preservation

MIBC patients who received NAC

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with localised muscle-invasive bladder cancer who received neoadjuvant chemotherapy

You may qualify if:

• Pathologically proven pure urothelial carcinoma, or morphologic variant of urothelial carcinoma.
• Patients with ≥T2, N0-1, M0, according to American Joint Committee on Cancer (AJCC) TNM Staging System for Bladder Cancer 8th ed., 2017.
• Patients who received platinum-based neoadjuvant chemotherapy before RC or BP.
• Available paraffin-embedded TUR specimens for Immunohistochemistry (IHC).

You may not qualify if:

• Non urothelial carcinoma.
• Not muscle invasive \< T2.
• Metastatic bladder cancer.
• No available paraffin-embedded TUR specimens for IHC.

Sponsors & Collaborators

• Assiut University: lead

Related Publications (12)

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  PMID: 30686350 RESULT

• Witjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, Ribal MJ, Van der Heijden AG, Sherif A; European Association of Urology. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014 Apr;65(4):778-92. doi: 10.1016/j.eururo.2013.11.046. Epub 2013 Dec 12.

  PMID: 24373477 RESULT

• Ikarashi D, Kitano S, Tsuyukubo T, Takenouchi K, Nakayama T, Onagi H, Sakaguchi A, Yamashita M, Mizugaki H, Maekawa S, Kato R, Kato Y, Sugai T, Nakatsura T, Obara W. Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting. Br J Cancer. 2022 Mar;126(4):606-614. doi: 10.1038/s41416-021-01628-y. Epub 2021 Nov 15.

  PMID: 34782748 RESULT

• Zhao J, Jin J. Neutrophil extracellular traps: New players in cancer research. Front Immunol. 2022 Aug 19;13:937565. doi: 10.3389/fimmu.2022.937565. eCollection 2022.

  PMID: 36059520 RESULT

• Kaltenmeier C, Yazdani HO, Morder K, Geller DA, Simmons RL, Tohme S. Neutrophil Extracellular Traps Promote T Cell Exhaustion in the Tumor Microenvironment. Front Immunol. 2021 Nov 24;12:785222. doi: 10.3389/fimmu.2021.785222. eCollection 2021.

  PMID: 34899751 RESULT

• Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007 Dec 6;450(7171):903-7. doi: 10.1038/nature06309. Epub 2007 Nov 18.

  PMID: 18026089 RESULT

• Durgeau A, Virk Y, Corgnac S, Mami-Chouaib F. Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy. Front Immunol. 2018 Jan 22;9:14. doi: 10.3389/fimmu.2018.00014. eCollection 2018.

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• Hadrup S, Donia M, Thor Straten P. Effector CD4 and CD8 T cells and their role in the tumor microenvironment. Cancer Microenviron. 2013 Aug;6(2):123-33. doi: 10.1007/s12307-012-0127-6. Epub 2012 Dec 16.

  PMID: 23242673 RESULT

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  PMID: 28131785 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

baseline formalin-fixed paraffin-embedded (FFPE) transurethral resection (TUR) biopsies

MeSH Terms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Amal R Ibrahim, Ass.Prof

  Assiut University

  STUDY DIRECTOR

• Hanan G Mostafa, Professor

  Assiut University

  STUDY DIRECTOR

Central Study Contacts

Gehad A Abdelrazik, ass.lecturer

CONTACT

01097381211; dr.gehadahmed95@gmail.com

Hebatullah M Bakri, Lecturer

CONTACT

01007272760; heba_bakri@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Study Record Dates

• First Submitted: March 16, 2024
• First Posted: March 22, 2024
• Study Start: April 1, 2024
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share