Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers

Официальное название

Tumor Microenvironment Features of Response to Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers

Обзор

The purpose of this study is to determine the safety of peri-operative gemcitabine, cisplatin, and pembrolizumab in patients with BTC, as well as whether the combination of gemcitabine, cisplatin, and pembrolizumab (gem/cis/pembro) is feasible and lead to pathologic responses.

Вмешательства

• Препарат Gemcitabine
  Patients will receive treatment on Day 1 and Day 8 of each cycle. Gemcitabine (1000 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.
• Препарат Cisplatin
  Patients will receive treatment on Day 1 and Day 8 of each cycle. Cisplatin (25 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.
• Препарат Pembrolizumab
  Patients will receive treatment on Day 1 of each cycle. Pembrolizumab (200 mg) will be administered IV on Day 1 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery. Pembrolizumab (400 mg) will be administered IV Q6 weeks up to 4 cycles as maintenance.

Первичные конечные точки

• Average minimum Euclidean distance from CD8+ T cells to immunosuppressive tumor-associated macrophages (TAMs) at the per-cell level in patients with a major pathologic response versus pathologic non-responders. [Срок оценки: 4 years]

Вторичные конечные точки (4)

• Number of participants experiencing grade 3 or above drug-related toxicities [Срок оценки: 4 years]
• Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility [Срок оценки: 144 days]
• Major pathologic response rate [Срок оценки: 8-12 weeks]
• R0 resection rate [Срок оценки: 60 days]

Критерии участия

Критерии включения

• Must have a newly diagnosed, biopsy-proven biliary tract cancer (BTC) including gallbladder, intrahepatic, extrahepatic, and hilar cholangiocarcinoma.
• Resectable BTC (biliary tract cancer)
• Measurable disease per RECIST 1.1 as determined by the investigator.
• Age ≥18 years.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤1 or Karnofsky ≥80
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Patients must have adequate liver function defined by study-specified laboratory tests.
• Patients with chronic or acute HBV or HCV infection must have disease controlled prior to enrollment.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Критерии исключения

• Receiving, or previously received, any systemic chemotherapy, or investigational agent for BTC.
• Has received prior radiotherapy within 2 weeks of start of study intervention.
• Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
• Have been diagnosed with another cancer or myeloproliferative disorder whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study's investigational drugs.
• Has a known history of Human Immunodeficiency Virus (HIV)/AIDS
• Has active co-infection with HBV and HDV.
• Has a diagnosis of immunodeficiency.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Systemic or topical corticosteroids at immunosuppressive doses.
• Prior allogeneic stem cell transplantation or organ transplantation.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation, including corneal transplants.
• Uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Evidence of clinical ascites.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Previously identified allergy or hypersensitivity to monoclonal antibodies or any component of the study treatment formulations.
• Pregnant or breastfeeding.
• WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
• Subjects unable to undergo venipuncture and/or tolerate venous access.
• Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• SKCCC Johns Hopkins — Baltimore

Идентификаторы

NCT: NCT06001658 · J2390 · IRB00371087

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗