Probiotics in Advanced Urothelial Carcinoma

Официальное название

A Multicenter, Randomized Controlled Phase II Study of Evaluating the Efficacy and Safety of Immunotherapy Combined With Oral Probiotics Compound (Biolosion) in Patients With Advanced Urothelial Carcinoma

Обзор

This is a multicenter, randomized, controlled phase II Study of evaluating the efficacy and safety of immunotherapy combined with probiotics compound (Biolosion) in patients with advanced urothelial carcinoma.

Подробное описание

This multicenter, randomized phase II trial is designed to study the efficacy and safety of probiotics compound (Biolosion) Immunotherapy of the physician's choice (IPC) plus versus IPC in patients with advanced urothelial carcinoma (aUC). Pervious received platinum-based therapies, previous received Immune checkpoint inhibitors, and the treatment lines will stratify randomization.

Вмешательства

• Препарат Probiotics Compound (Biolosion)
  15g, PO, qd
• Препарат Nab-paclitaxel
  230mg/m2, IV, days 1, 8, q3w
• Препарат Cisplatin
  70mg/m2, IV, days 1-3, q3w
• Препарат Gemcitabine
  1.2g/m2, IV, days 1, 8, q3w
• Препарат Disitamab vedotin
  2.5mg/kg, IV, q2w
• Препарат Enfortumab Vedotin
  1.25mg/kg, IV, days 1, 8, q3w
• Препарат Pembrolizumab
  200mg, IV, q3w
• Препарат Toripalimab
  240mg, IV, q3w

Первичные конечные точки

• Progression-free Survival (PFS) [Срок оценки: Within approximately 48 months]

Вторичные конечные точки (6)

• Overall Survival (OS) [Срок оценки: Within approximately 48 months]
• Objective Response Rate (ORR) [Срок оценки: Within approximately 48 months]
• Disease Control Rate (DCR) [Срок оценки: Within approximately 48 months]
• Time to Response (TTR) [Срок оценки: Within approximately 48 months]
• Duration of Response (DOR) [Срок оценки: Within approximately 48 months]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Срок оценки: Within approximately 48 months]

Критерии участия

Критерии включения

• Patients included in this study must meet all of the following criteria:

• Aged 18 or above;
• Histologically or cytologically confirmed locally advanced inoperable (such as T4b, or N2-3) or metastatic urothelial carcinoma, including bladder, ureter, renal pelvis and urethra;
• Patients who have received previous treatment with immune checkpoint inhibitors (PD-1/PD-L1 monoclonal antibodies) are allowed;
• According to RECIST1.1 standard, there is at least one measurable target lesion;
• ECOG score ≤2;
• Good bone marrow, kidney (serum creatinine clearance calculated by CG formula> 30 mL/min), liver and coagulation function:
• Expected survival period ≥ 6 months;
• The patient understands the research procedures and signs the informed consent form in writing to indicate his/her agreement to participate in the study;
• Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 7 days before the first dose of study drug (Cycle 1, Day 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required.
• If there is a risk of pregnancy, male and female patients should use highly effective contraception (i.e., a method with a failure rate of less than 1% per year) and continue for at least 180 days after stopping the trial treatment.

Критерии исключения

• Any of the following will be considered as meeting the exclusion criteria of the study:

• Patients with locally advanced disease may receive local radical treatment;
• History of clinically symptomatic cardiovascular, liver, respiratory, renal, hematoendocrine, or neuropsychiatric diseases;
• Clear brain/meningeal metastasis;
• Peripheral neuropathy >1 degree;
• Patients who have received anti-tumor monoclonal antibody treatment within 4 weeks before the start of the study, or have received other anti-tumor drug treatment and have not recovered from adverse events/reactions;
• Participated in any investigational drug treatment within 4 weeks before the start of treatment;
• Patients who had received axial bone radiotherapy within 4 weeks before the start of the study or had not recovered from adverse reactions caused by previous radiotherapy;
• Known severe allergic reaction to the study drug, its active ingredients and/or any excipients;
• Patients diagnosed with immunodeficiency or receiving systemic glucocorticoids or any other form of immunosuppressive therapy within 7 days before the first dose of the study; physiological doses of glucocorticoids (≤10 mg/day of prednisone or equivalent drugs) are allowed;
• Active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) occurred within 2 years before the first dose. Replacement therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment; a history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before the first dose or current interstitial lung disease;
• Received solid organ or blood system transplantation;
• Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive). Untreated active hepatitis B;
• Untreated active hepatitis B; Note: Hepatitis B subjects who meet the following criteria are also eligible for inclusion: HBV viral load must be <1000 copies/ml (200 IU/ml) before the first dose, and subjects should receive anti-HBV treatment during the entire study chemotherapy treatment to avoid viral reactivation. For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), preventive anti-HBV treatment is not required, but viral reactivation needs to be closely monitored;
• Subjects with active HCV infection (HCV antibody positive and HCV-RNA level above the detection limit) received live vaccine within 30 days before the first dose (Cycle 1, Day 1);
• A history of other malignant tumors in the past 5 years, excluding cured non-malignant melanoma of the skin, cervical carcinoma in situ, and incidentally discovered prostate cancer (stage lower than T2N0M0, Gleason score <7, or undetectable PSA);
• Medical history or disease evidence, abnormal treatment or laboratory test values, or other conditions that the researcher considers unsuitable for enrollment that may interfere with the trial results or prevent the subject from fully participating in the study;
• Breastfeeding women
• People with chronic diseases who need to take antibiotics for a long time.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Sun yat-sen university cancer center — Гуанчжоу
• Sun Yat-sen Memorial Hospital — Гуанчжоу
• Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology — Ухань

Публикации

• Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, Frankel P, Cui Y, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Highlander SK, Pal SK. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a ra PMID 35228755
• Miyake M, Oda Y, Owari T, Iida K, Ohnishi S, Fujii T, Nishimura N, Miyamoto T, Shimizu T, Ohnishi K, Hori S, Morizawa Y, Gotoh D, Nakai Y, Torimoto K, Tanaka N, Fujimoto K. Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer. Cancer Sci. 2023 Mar;114(3):1118-1130. doi: 10.1111/cas.15666. Epub 2022 Nov 30. PMID 36398663
• Messaoudene M, Pidgeon R, Richard C, Ponce M, Diop K, Benlaifaoui M, Nolin-Lapalme A, Cauchois F, Malo J, Belkaid W, Isnard S, Fradet Y, Dridi L, Velin D, Oster P, Raoult D, Ghiringhelli F, Boidot R, Chevrier S, Kysela DT, Brun YV, Falcone EL, Pilon G, Onate FP, Gitton-Quent O, Le Chatelier E, Durand S, Kroemer G, Elkrief A, Marette A, Castagner B, Routy B. A Natural Polyphenol Exerts Antitumor Ac PMID 35031549
• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5. PMID 26541606
• Li WT, Iyangar AS, Reddy R, Chakladar J, Bhargava V, Sakamoto K, Ongkeko WM, Rajasekaran M. The Bladder Microbiome Is Associated with Epithelial-Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma. Cancers (Basel). 2021 Jul 21;13(15):3649. doi: 10.3390/cancers13153649. PMID 34359550
• Grande E, G.M., Arranz Arija JA, et al., IMvigor130: a phase III study of atezolizumab with or without platinum-based chemotherapy in previously untreated metastatic urothelial carcinoma. Presented at: . ESMO Congress; , 2019 Abstract LBA14.
• Lichtenegger FS, Rothe M, Schnorfeil FM, Deiser K, Krupka C, Augsberger C, Schluter M, Neitz J, Subklewe M. Targeting LAG-3 and PD-1 to Enhance T Cell Activation by Antigen-Presenting Cells. Front Immunol. 2018 Feb 27;9:385. doi: 10.3389/fimmu.2018.00385. eCollection 2018. PMID 29535740
• Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, Chaput N, Eggermont A, Marabelle A, Soria JC, Ferte C. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res. 2017 Apr 15;23(8):1920-1928. doi: 10.1158/1078-0432.CCR-16-1741. Epub 2016 Nov 8. PMID 27827313

Идентификаторы

NCT: NCT06904573 · 2024-FXY-297

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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