Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers
- Conditions
- Billiary Track Cancer
- Interventions
- Registration Number
- NCT06001658
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 27
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Gemcitabine, Cisplatin and Pembrolizumab Gemcitabine - Gemcitabine, Cisplatin and Pembrolizumab Cisplatin - Gemcitabine, Cisplatin and Pembrolizumab Pembrolizumab -
- Primary Outcome Measures
Name Time Method 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. 4 years The evaluable population of this endpoint consist of all patients who receive at least one dose of study drug and have TAMs and CD8 T cell measures at the time of surgery. TAMs being evaluated are the following: immunosuppressive TAMs with high Arginase-1 expression (CD68+CD163+Arg-1hiPDL1-/+), immunosuppressive TAMs with low Arginase-1 expression (CD68+CD163+Arg-1lo PDL1-/+), and less immunosuppressive TAMs (CD68+CD163-HLA-DRhi/CD86hi/PDL1hi)
- Secondary Outcome Measures
Name Time Method Number of participants experiencing grade 3 or above drug-related toxicities 4 years When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.
Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility 144 days Extended treatment delay is defined as a delay of greater than 60 days of the pre-planned surgical evaluation date, or inability to go to surgery due to an adverse event related to study treatment.
R0 resection rate 60 days The number of participants with a R0 resection as defined by a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.
Major pathologic response rate 8-12 weeks The number of participants with a major pathologic response as defined by ≤ 10% residual viable tumor cells in the resection of the primary tumor and lymph nodes.
Trial Locations
- Locations (1)
SKCCC Johns Hopkins
🇺🇸Baltimore, Maryland, United States