Phase Ib/II Trial of Nal-Irinotecan and Nivolumab as Second-Line Treatment in Patients With Advanced Biliary Tract Cancer

Study Name
	Phase Ib/II Trial of Nal-Irinotecan and Nivolumab as Second-Line Treatment in Patients With Advanced Biliary Tract Cancer
ClinicalTrials.gov Identifier (if applicable)
	NCT03785873
Clinical Trial Category (check all that apply)
	Beyond First Line Therapy Chemotherapy Immunotherapy
Study Center
Institution Name
	University of Michigan
Institution Address
	1500 E Medical Center Dr
City
	Ann Arbor
State
	Michigan
Zip Code
	48109
Country
	United States
Phone
	(800) 865-1125
Website
	https://clinicaltrials.gov/ct2/show/NCT03785873
List additional Institutions (include address, phone number, and website)
	Due to open at: University of Wisconsin University of California, San Diego Cancer and Hematology Centers of Western Michigan, Grand Rapids
Study Contacts
Principal Investigator
	Vaibhav Sahai
P.I. Phone
	(734) 936-4991
P.I. Email
	vsahai@umich.edu
Study Coordinator
	Alexander Pifer
Study Coordinator Phone
	(800) 865-1125
Study Coordinator Email
	apifer@med.umich.edu
OVERVIEW – in layman’s terms (150 words max)
	All patients on this study receive the chemotherapy combination of 5-FU, leucovorin and nanoliposomal irinotecan which has shown efficacy in pancreatic cancer (and is FDA approved). In addition, this trial adds immunotherapy (nivolumab) to this chemotherapy regimen to leverage the synergism of chemo-immunotherapy.
Enrollment
	32
Study Start Date
	05/01/2019
Estimated Completion Date
	10/31/2020
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
	Improve the efficacy of patients with biliary tract cancer
Inclusion Criteria – Patients Must:
	Patients must have a pathologically confirmed carcinoma of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gall bladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors with mixed hepatocellular and cholangiocarcinoma histology are excluded. Patients must have received one and only one prior systemic therapy for advanced disease. Prior therapies must have not included irinotecan or PD- 1/PD-L1 antibody. Patient should have either progressed on or within 6 months of first-line systemic therapy or deemed intolerant of that therapy. Prior surgical resection, radiation, chemoembolization, radioembolization or other local ablative therapies are permitted if completed ≥ 4 weeks prior to registration AND if patient has recovered to ≤ grade 1 toxicity. Patients must have radiographically measurable disease (as per RECISTv1.1) in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic lesion. Age ≥18 years Child-Pugh score of less than 7 ECOG performance status of 0-1 Ability to understand and willingness to sign IRB-approved informed consent Available archived tissue (FFPE block or 20 unstained slides from prior core biopsy or surgery) Must be able to tolerate CT and/or MRI with contrast Adequate organ function (per protocol) assessed ≤2 weeks prior to registration
Exclusion Criteria – Patients Must NOT:
	Must not have received systemic steroid therapy, or any other form of immunosuppressive therapy within 14 days prior to registration. Short bursts of steroids of 5-7 days (for COPD exacerbation or other similar indication) are allowed. No prior history of solid organ transplantation or brain metastasis (unless treated, asymptomatic and stable). Must not have undergone a major surgical procedure < 4 weeks prior to registration. Must not have an active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ. Patients with history of malignancy are eligible provided primary treatment of that cancer was completed > 1 year prior to registration and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy. Must have no ongoing active, uncontrolled infections (afebrile for > 48 hours off antibiotics). Must not have received a live vaccine within 30 days of registration Must not have a psychiatric illness, other significant medical illness, or social situation which, in the investigator’s opinion, would limit compliance or ability to comply with study requirements. Women must not be pregnant or breastfeeding since 5-fluorouracil, nal- irinotecan and/or nivolumab may harm the fetus or child. All females of childbearing potential (not surgically sterilized and between menarche and 1- year post menopause) must have a blood test to rule out pregnancy within 2 weeks prior to registration. Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation, and for 5 months (for women) and 7 months (for men) following completion of study therapy. Participants with an active, known or suspected autoimmune disease which may affect vital organ function, or has/may require systemic immunosuppressive therapy for management are excluded. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of registration are excluded. Inhaled, ocular, intra-articular, intra-nasal or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. No known UGT1A1* variants or Gilbert’s syndrome Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness would be excluded. No known hypersensitivity to 5-fluorouracil, leucovorin, irinotecan, and/or nivolumab. Must not have ongoing bowel obstruction. No known HIV, Hepatitis B or Hepatitis C infection that is untreated and/or with a detectable viral load. Patients must not have uncontrolled intercurrent illness including, but not limited to, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia. No known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator’s opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results. Patients must not be on warfarin, strong CYP3A4 inducers (such as phenytoin, phenobarbital, primidone, carbamazepine, rifampin, rifabutin, rifapentine or St. John’s wort), strong CYP3A4 inhibitors (such as ketoconazole, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole), and strong UGT1A1 inhibitors (such as atazanavir, gemfibrozil, indinavir and ketoconazole).
REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT – in layman’s terms
	Blood tests and CAT scans
POTENTIAL SIDE-EFFECTS – in layman’s terms
	Chemotherapy potential side effects (such as nausea, tiredness, low blood counts, diarrhea) as well as Immunotherapy side effects (such as inflammation of an organs which can lead to skin rash, diarrhea, elevated liver enzymes, tiredness, thyroid dysfunction, shortness of breath).