Billiary Track Cancer
Conditions
Keywords
Biliary Tract cancer, Pembrolizumab, Gemcitabine, Cisplatin, Immunotherapy, Potentially resectable biliary tract cancer, Anti PD-L1, PD-L1, Carcinoma
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.
Interventions
DRUGGemcitabine
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.
DRUGCisplatin
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.
DRUGPembrolizumab
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.
Sponsors
Merck Sharp & Dohme LLC
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
Primary ContactColleen Apostal, RN
Outcome results
None listed