Study of the Combination of DKN-01 and Nivolumab in Previously Treated Patients With Advanced Biliary Tract Cancer (BTC)

  • End date
    Aug 31, 2024
  • participants needed
  • sponsor
    Massachusetts General Hospital
Updated on 21 February 2022
systemic therapy
measurable disease
international normalized ratio
neutrophil count
liver metastasis
radiofrequency ablation
advanced biliary tract carcinoma
extrahepatic cholangiocarcinoma
biliary tract cancer


This research is studying the effect of the combination of how two study drugs (Nivolumab and DKN-01) works in people with advanced biliary tract cancer.


This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved DKN-01 as a treatment for any disease.

The FDA has not approved nivolumab for this specific disease but it has been approved for other cancers.

DKN-01 and nivolumab are both antibodies. An antibody is a protein that attaches to other cells to fight off infection. DKN-01 is believed to work by attaching to and inhibiting (stopping) a specific pathway in the cells that is responsible for processes such as cell growth. Nivolumab is believed to work by attaching to and inhibiting a specific protein in the cancer that controls parts of the immune system (the system in the body that fights off infections and diseases) by shutting down certain immune responses. The investigators believe that nivolumab will inhibit the protein, thus allowing the immune cells to recognize and destroy cancer cells.

Condition Biliary Tract Cancer
Treatment Nivolumab, DKN-01
Clinical Study IdentifierNCT04057365
SponsorMassachusetts General Hospital
Last Modified on21 February 2022


Yes No Not Sure

Inclusion Criteria

Histologically confirmed intra- or extrahepatic cholangiocarcinoma or gallbladder cancer
Participants must have measurable disease by CT/MRI by RECIST version 1.1 criteria
Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside of the treated area or measurable progression per RECIST v1.1 at the site of the treated area
Documented progression after 1 line of systemic therapy for advanced BTC. Prior adjuvant chemotherapy qualifies as this 1 line if the last cycle of adjuvant therapy was completed within 6 months of radiological progression
Age 18 years
ECOG performance status 1
Life expectancy of greater than 3 months
Participants must have normal organ and marrow function as defined 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
Subjects with hepatitis B or C are eligible to enroll if they have
Chronic HBV infection (evidenced by a positive HBV surface antigen or HBV DNA) as long as they have been on antiviral therapy for 4 weeks
Chronic or resolved HCV infection (evidenced by a detectable HCV RNA or antibody). Antiviral therapy is not required for chronic HCV
Women of child-bearing potential and men must agree to use adequate contraception according to national guidelines (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months for women and 7 months for men after completion of study drug administration
Female subjects must be either of non-reproductive potential (i.e., post-menopausal by history: 50 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Prior DKK1 inhibitor or anti-PD-1/PD-L1 treatment
Participants with Child-Pugh B or C cirrhosis
Participants with a diagnosis of ampullary cancer
Treatment with any of the following within the specified time frame prior to the first dose of DKN-01 and nivolumab
Any non-investigational or investigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to treatment administration (mitomycin within prior 5 weeks). For targeted therapy, 5 half-lives are sufficient, even if <3 weeks. Concurrent participation in an observational study may be allowed after review by the Principal Investigator
Patients with locoregional therapy, e.g., transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT), external beam radiation, or ablation within 4 weeks
Palliative limited field radiotherapy (i.e. bone metastases) within 2 weeks
Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of treatment)
Fredericia's corrected QT interval (QTcF) 500 ms on ECG conducted during screening
History of allergic reactions attributed to compounds of similar chemical or biologic composition to DKN-01 or Nivolumab
A serious illness or medical condition(s) including, but not limited to, the
Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for 1 month without systemic corticosteroids beyond physiologic replacement (>10 mg prednisone daily)
Known acute systemic infection
Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure
New York Heart Association [NYHA] Class III or IV (see Appendix D, New York Heart Association [NYHA] Classification) within the previous 2 months; if >2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms
Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator
Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the investigator would make the patient inappropriate for entry into this study
Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention (except for hormonal therapy for breast or prostate cancer)
Any condition requiring systemic treatment with either corticosteroids (> 2mg daily dexamethasone equivalent) or other immunosuppressive medications within 14 days of starting the study medications. Premedication for hypersensitivity reactions (e.g. to contrast for CT or gadolinium for MRI) is allowed
Subjects with autoimmune disease active within the last two years including but not limited to Crohn's disease, ulcerative colitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjgren's syndrome, Guillain-Barr syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis
Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study
Patients with controlled Type I diabetes mellitus on a stable insulin regimen are eligible
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis/fibrosis in the radiation field is permitted
Patients who received treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, seasonal flu, H1N1 flu, rabies, BCG and typhoid vaccine
History of osteonecrosis of the hip or evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that is symptomatic and clinically significant. Degenerative changes of the hip joint are not excluded
Known osteoblastic bony metastasis. Screening of asymptomatic subjects without a history of metastatic bony lesions is not required
Prior allogeneic stem cell or solid organ transplant
Known or current evidence of HIV
Pregnant or lactating female
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