A Phase 2 Single-arm Study of Cemiplimab, Added to Typical Chemotherapy (Gemcitabine, Cisplatin, Nab-paclitaxel) for Down-staging of Locally Advanced, Unresectable Biliary Tract Cancer
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Columbia University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Rate of conversion to resectable disease and subsequent surgical resection
Overview
Brief Summary
This study is being conducted to find out if treatment with gemcitabine, cisplatin, nab-paclitaxel, and cemiplimab can shrink previously inoperable tumors enough for surgery.
Detailed Description
The purpose of this study is to combine chemotherapy that has previously been shown to have activity in patients with biliary tract cancer with a drug that stimulates the body's immune system against cancer cells (immunotherapy). Previously, the combination of gemcitabine and cisplatin with immunotherapy has been shown to prolong life in patients with advanced biliary tract cancer. Adding nab-paclitaxel, another chemotherapy, to gemcitabine and cisplatin, has also been shown to prolong life in some patients with advanced biliary tract cancer. However, all four of these drugs have not before been combined. Cemiplimab is being used in an investigational manner (not for the purpose that it was approved for) in this research study. This means that cemiplimab has been approved by the Food and Drug Administration (FDA) for use in advanced or metastatic cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer, but has not been approved for locally advanced biliary tract cancer that cannot be surgically removed. Since surgery is the only way to potentially cure this cancer, new treatments are needed that can shrink inoperable tumors enough to make surgery possible. This is especially important for patients with advanced biliary tract cancer that hasn't spread to other parts of the body.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed diagnosis of biliary tract adenocarcinoma (intra- or extra-hepatic, and gallbladder)
- •Locally advanced, unresectable BTC without evidence of distant metastatic disease. Patients with surgically unresectable BTC on diagnostic abdominal CT scan or MRI are eligible to participate in the study. Unresectable, locally advanced, but non-metastatic BTC must be confirmed with the designated site radiologist and surgeon at the treating institution (Appendix 2) and must meet at least one of the following criteria:
- •Tumor involvement of both hepatic lobes and/or vessels
- •Vascular invasion of the portal vein or main hepatic artery
- •For perihilar tumors: bilateral hepatic duct involvement up to secondary radicles
- •Atrophy of one liver lobe with invasion of contralateral vessel and/or bile duct
- •Extrahepatic organ tumor invasion, except contiguous involvement of the diaphragm
- •Inadequate estimated liver remnant after surgery If resectability cannot be determined based on CT or MRI, an FDG-PET may be performed, and if it cannot be determined based on imaging alone, surgical exploration is permitted.
- •Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of cemiplimab added to gemcitabine, cisplatin, and nab-paclitaxel in participants \<18 years of age, children are excluded from this study.
- •Treatment naïve; no prior systemic therapy
Exclusion Criteria
- •Histologies other than adenocarcinoma such as mixed hepatocellular carcinoma/cholangiocarcinoma, adenosquamous carcinoma or mixed adenocarcinoma/neuroendocrine carcinoma; ampullary carcinomas are also excluded.
- •Has initially resectable disease or distant metastasis, including distant lymph nodes.
- •Resectable BTC include the following: absence of retropancreatic and paraceliac nodal metastases or distant liver metastases, absence of invasion of the portal vein or main hepatic artery, absence of extrahepatic adjacent organ invasion, absence of disseminated disease.
- •Participants may not have had systemic chemotherapy, investigational therapy, or treatment with T-cell co-stimulating or immune check point blockade therapies (including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic antibodies) prior to initiation of study treatment.
- •Participants receiving any other investigational agents concurrently or other anti-neoplastic agents (hormone therapy acceptable)
- •Participants may not have had previous radiotherapy for the biliary tract tumor.
- •Patients may not have had surgical resection of biliary tract cancer prior to initiation of study intervention.
- •Participants may not have undergone major surgery or experienced significant traumatic injury within 14 days prior to initiating study treatment or be recovering from procedure-related adverse events of \> Grade
- •An active autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
- •Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
Arms & Interventions
Cemiplimab
All study participants will receive cemiplimab in addition to chemotherapy drugs (gemcitabine, cisplatin, and nab-paclitaxel).
Intervention: Cemiplimab (Drug)
Outcomes
Primary Outcomes
Rate of conversion to resectable disease and subsequent surgical resection
Time Frame: 6 months from start of study treatment
Successful conversion to resectable disease must meet all of the following criteria: * Absence of extra-regional lymph node metastases, including retropancreatic or paraceliac lymph node involvement * Absence of invasion of the portal vein or main hepatic artery * Absence of extrahepatic organ tumor invasion, except for contiguous involvement of the diaphragm * Absence of bilobar liver involvement, including bilateral bile duct involvement to the secondary radicles * If right or left hepatic lobe atrophy, absence of contralateral secondary biliary radicle involvement * Absence of disseminated metastatic disease * Adequate estimated liver remnant after surgery (This may be achieved with portal vein embolization.) * Tumor resected.
Secondary Outcomes
- Rate of R0 resection(up to 5 years)
- Time to resection(up to 5 years)
- Objective Response Rate (ORR)(up to 5 years)
- Median recurrence-free survival (mRFS) from the time of resection until histologic confirmation of recurrent BTC(up to 5 years)
- Median overall survival (mOS) from the start of chemotherapy with added cemiplimab therapy until death from any cause(up to 5 years)
- The rate of Grade ≥ 3 adverse events(throughout study treatment period (up to 5 years) and up to 90 days thereafter)
- The rate of study treatment discontinuation due to adverse events(up to 5 years)
Investigators
Linda Wu
Assistant Professor of Medicine
Columbia University