Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Gemcitabine, Cisplatin and Pembrolizumab
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Drug: 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.
Drug: 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.
Drug: 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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Must have a newly diagnosed, biopsy-proven biliary tract cancer (BTC) including gallbladder, intrahepatic, extrahepatic, and hilar cholangiocarcinoma.
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Resectable BTC (biliary tract cancer)
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Measurable disease per RECIST 1.1 as determined by the investigator.
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Age ≥18 years.
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ECOG (Eastern Cooperative Oncology Group) performance status ≤1 or Karnofsky ≥80
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Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
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Patients must have adequate liver function defined by study-specified laboratory tests.
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Patients with chronic or acute HBV or HCV infection must have disease controlled prior to enrollment.
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Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
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For both Women and Men, must use acceptable form of birth control while on study.
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Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
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Receiving, or previously received, any systemic chemotherapy, or investigational agent for BTC.
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Has received prior radiotherapy within 2 weeks of start of study intervention.
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Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
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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.
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Has a known history of Human Immunodeficiency Virus (HIV)/AIDS
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Has active co-infection with HBV and HDV.
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Has a diagnosis of immunodeficiency.
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Has active autoimmune disease that has required systemic treatment in the past 2 years.
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Systemic or topical corticosteroids at immunosuppressive doses.
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Prior allogeneic stem cell transplantation or organ transplantation.
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Prior tissue or organ allograft or allogeneic bone marrow transplantation, including corneal transplants.
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Uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
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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.
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Evidence of clinical ascites.
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Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
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Previously identified allergy or hypersensitivity to monoclonal antibodies or any component of the study treatment formulations.
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Pregnant or breastfeeding.
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WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
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Subjects unable to undergo venipuncture and/or tolerate venous access.
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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).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | SKCCC Johns Hopkins | Baltimore | Maryland | United States | 21231 |
Sponsors and Collaborators
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Marina Baretti, M.D., SKCCC Johns Hopkins Medical Institution
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- J2390
- IRB00371087