Anti-PD-1/PD-L1 Antibodies Plus Gemcitabine and Cisplatin for Advanced CCA

Официальное название

A Phase I/II Study of Anti-PD-1/PD-L1 Antibodies in Combination With Gemcitabine and Cisplatin for Patients With Advanced Cholangiocarcinoma

Обзор

This study is a prospective, observational study designed to analyze the safety, tolerability, and efficacy of first-line treatment using the combination of gemcitabine and cisplatin plus anti-PD-1/PD-L1 antibodies for patients with advanced cholangiocarcinoma.

Подробное описание

This is a prospective cohort study of combination anti-PD-1/PD-L1 antibodies plus Gemcitabine and Cisplatin chemotherapy for adult patients (≥18) with advanced cholangiocarcinoma

Gemcitabine and Cisplatin (GC): This chemotherapy doublet has been the historical standard of care for advanced cholangiocarcinoma. It works by interfering with DNA synthesis and causing DNA cross-linking, leading to tumor cell apoptosis.

Anti-PD-1/PD-L1 antibodies: Immunotherapy (including pembrolizumab, durvalumab, envafolimab, tislelizumab, etc.) is designed to block the PD-1/PD-L1 immune checkpoint pathway, thereby reinvigorating T-cells to recognize and attack tumor cells. Recent pivotal trials (e.g., TOPAZ-1, KEYNOTE-966) have demonstrated that adding immunotherapy to GC chemotherapy significantly improves overall survival compared to chemotherapy alone.

This study aims to evaluate the real-world safety, tolerability, and clinical efficacy of this combination regimen in specific clinical practice settings for unresectable late-stage cholangiocarcinoma patients.

Вмешательства

• Препарат Anti-PD-1/PD-L1 antibody
  Anti-PD-1/PD-L1 Intravenous injection for at least 6 months
• Препарат Gemcitabine and Cisplatin Chemotherapy
  Gemcitabine and cisplatin Intravenous injection for at least 6 months

Первичные конечные точки

• Incidence of adverse events [Срок оценки: Up to 30 days after last treatment dose]
• Objective response rate(ORR) [Срок оценки: 5 years]
• Progression free survival(PFS) [Срок оценки: 5 years]
• To the relief time (TOR) [Срок оценки: Time Frame: 5 years]
• Duration of relief(DOR) [Срок оценки: 5 years]
• Disease Control Rate (DCR) [Срок оценки: Time Frame: 5 years]

Критерии участия

Критерии включения

• 1\. ≥18 years old, male or female 2. Histologically or cytologically confirmed locally advanced or metastatic biliary tract cancer (including ICC, ECC, or GBC) that is not amenable to curative surgery or local therapies.

3\. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 4. Patient has given written informed consent. 5. The function of important organs meets the requirements 6. Expected survival ≥12 weeks 7. Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period.

Критерии исключения

• 1\. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included); 2. The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment; 3. Have clinical symptoms or disease that are not well controlled; 4. Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization; 5. Arterial/venous thrombosis in the first 6 months of randomization 6. According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.#with family or social factors, it will affect the safety of patients. 7. Known hypersensitivity to Gemcitabine, Cisplatin, or platinum-containing compounds; significant hearing impairment (grade ≥2) or peripheral neuropathy (grade ≥2) that contraindicates Cisplatin;

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

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Zhongshan Hospital Fudan university — Шанхай

Публикации

• Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1 PMID 38319896
• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721. PMID 20375404
• Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a PMID 37075781

Идентификаторы

NCT: NCT07291063 · Y2024-752

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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