A Single Arm Phase II Study of the Combination of DKN-01 and Nivolumab in Previously Treated Patients with Advanced Biliary Tract Cancer (BTC)

Study Name
	A Single Arm Phase II Study of the Combination of DKN-01 and Nivolumab in
ClinicalTrials.gov Identifier (if applicable)
	NCT04057365
Clinical Trial Category (check all that apply)
	Beyond First Line Therapy Targeted Therapy Immunotherapy
Study Center
Institution Name
	Massachusetts General Hospital Cancer Center
Institution Address
	55 Fruit St
City
	Boston
State
	Massachusetts
Zip Code
	02114
Country
	United States
Phone
	(617) 726-2000
Website
	http://www.massgeneral.org
List additional Institutions (include address, phone number, and website)
	Dana-Farber Cancer Institute 450 Brookline Ave Boston, Massachusetts 02215 617-632-3000 http://www.dana-farber.org
Study Contacts
Principal Investigator
	Lipika Goyal, MD
P.I. Phone
	(617) 724-4000
List additional Principal Investigators (include phone number and email)
	Dana- Farber Site PI: Thomas Abrams 617-632-6932 Thomas_Abrams@dfci.Harvard.edu
Study Coordinator
	Patricia Lynch
Study Coordinator Phone
	(617) 643-0816
Study Coordinator Email
	Lynch.Patricia2@mgh.harvard.edu
OVERVIEW – in layman’s terms (150 words max)
	Patients who have already undergone another systemic therapy will be treated with DNK-01 and Nivolumab IV every two weeks.
Enrollment
	30
Study Start Date
	10/02/2019
Estimated Completion Date
	08/31/2024
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
	Evaluate how patients with advanced biliary tract cancer respond to the combination of DNK-01 and nivolumab together. Evaluate how safe and tolerable it is for patients with biliary tract cancer to take both DNK-01 and nivolumab at the same time. Evaluate the average amount of time patients are tumor free and survive overall while on the therapy Evaluate how different genes affect the response of the tumor and overall survival of patients on therapy Explore how different mutations in blood, tissue and stool relate to the treatment
Inclusion Criteria – Patients Must:
	Intra or Extrahepatic Cholangiocarcinoma or gallbladder cancer (confirmed with tumor tissue) Tumor progression on scans after at least 1 other systemic treatment for advanced biliary tract cancer. Prior secondary treatment of chemotherapy qualifies as first line if the last cycle was completed within 6 months of progression on scans Have measurable tumors on scans (CT or MRI) Prior treatment to the liver, if there is still tumor outside of the region that was treated or if the tumor returned ECOG performance score of 0 or 1 Life expectancy greater than 3 months Normal organ function determined through blood tests below: Absolute neutrophil count ≥1,500/mcL Absolute lymphocyte count ≥1.0 x 10^9/L Platelets ≥75,000/mcL Hemoglobin ≥ 8.0 g/dL (prior transfusions are allowed if given ≥ 7 days before testing Total bilirubin < 2.0 x institutional upper limit of normal; except patients with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal; < 5 x ULN in case of liver metastases Creatinine < 2.0 x institutional upper limit of normal OR Creatinine clearance ≥30 mL/min/1.73 m2 for participants with creatinine levels ≥ ULN International Normalized Ratio (INR) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as INR is within therapeutic range of intended use of anticoagulants Serum albumin > 2.5 g/dL
Exclusion Criteria – Patients Must NOT:
	Prior DKK1 inhibior or anti PD-1/PD-L1 treatment Child Pugh B or C cirrhosis Non-investigational or investigational anticancer therapy within 3 weeks Targeted therapy within 5 half lifes Locoregional therapy within 4 weeks Palliative limited field radiotherpay within 2 weeks Major surgery within 4 weeks (incision must be healed) Screening ECG with a Fredericia’s corrected QT interval 500 or greater Known brain metastasis (not including primary tumors) unless patient is clincially stable for more than 1 month without systemic Condition requiring systemic corticosteroid treatment (>2mg daily of dexamethasone equivalent) or immunosuppressive medicaiton within 14 days Autoimmune disease active within the last 2 years — patients hypothyroidism on a stable thyriod hormone replacement and/or type I diabetes mellitus on a stable insulin regiment are eligible
REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT – in layman’s terms
	Physical Exam / Appointment with Doctor Blood Test EKG CT and/or MRI Pregnancy Test (women of child-bearing potential only) Tumor Biopsy – if doctor feels it is safe
POTENTIAL SIDE-EFFECTS – in layman’s terms
	Nausea Vomiting Decreased Appetite Joint Pains Fatigue Itching