Clinical trial NCT06001658: Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers
Official title: Tumor Microenvironment Features of Response to Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Billiary Track Cancer
Keywords: Biliary Tract cancer
Pembrolizumab
Gemcitabine
Cisplatin
Immunotherapy
Potentially resectable biliary tract cancer
Anti PD-L1
PD-L1
Carcinoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2023-08-21
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: 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.
timeFrame: 4 years
Secondary outcomes:
measure: Number of participants experiencing grade 3 or above drug-related toxicities
timeFrame: 4 years
measure: Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility
timeFrame: 144 days
measure: Major pathologic response rate
timeFrame: 8-12 weeks
measure: R0 resection rate
timeFrame: 60 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: SKCCC Johns Hopkins
state: Maryland
Study officials:
affiliation: SKCCC Johns Hopkins Medical Institution
name: Marina Baretti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: