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Biliary Tract CancerPhase 2NCT04057365

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

A Phase 2 study testing Nivolumab and DKN-01 in people with Biliary Tract Cancer, run by Massachusetts General Hospital at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer
What is being tested?
Nivolumab and DKN-01
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
7 Oct 2019to 25 Sep 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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 following:
  • 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, Sjögren's syndrome, Guillain-Barré 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
Nivolumab, DKN-01
Keywords
Biliary Tract Cancer
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo

    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.

  • DKN-01Drug

    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

Study groups in NCT04057365
Study groupRoleWhat they receive
DKN 01 and Nivolumab Safety Run inExperimental* DKN-01 will be administered intravenously on day 1 and day 15 of each 28 day cycle * Nivolumab will be administered intravenously on day 1 and day 15 of each 28 day cycle
Receives: Drug: Nivolumab; Drug: DKN-01
DKN 01 and NivolumabExperimental* DKN-01 will be administered intravenously on day 1 and day 15 of each 28 day cycle * Nivolumab will be administered intravenously on day 1 and day 15 of each 28 day cycle
Receives: Drug: Nivolumab; Drug: DKN-01

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate

    Overall response is evaluated using Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). A participant is considered to have responded if they achieve either of the following outcomes:

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm
    • Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

    Measured: up to 1 year

Secondary outcomes (3)

  1. Progression Free Survival

    Progression-Free Survival (PFS) is defined as the time from registration to the earlier of disease progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.

    Disease progression is assessed using RECIST 1.1 criteria:

    • Progressive Disease(PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Measured: up to 1 year

  2. Overall Survival

    Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive.

    Measured: up to 1 year

  3. Treatment Emergent Adverse Events

    Treatment emergent adverse events (TEAEs) are undesirable events not present prior to study treatment, or an already present event that worsens either in intensity or frequency following the treatment. TEAEs reported below were assessed as grade 3 or higher according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 5.0) guidelines.

    Measured: up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2019
  2. Study start7 Oct 2019
  3. Primary completion25 Sep 2022
  4. Study completion25 Sep 2022

Why it stopped: Based on a Simon 2-stage design, this study did not meet response criteria to proceed to stage 2.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04057365
Sponsor's protocol ID
19-200
Status last verified
Aug 2025
First submitted
13 Aug 2019
Last updated
13 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and DKN-01 in people with Biliary Tract Cancer, run by Massachusetts General Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (time frame: up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04057365.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2025.

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