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

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Brief Title

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

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)

Brief 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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response Rate

Secondary Outcome

 Median Progression Free Survival

Condition

Biliary Tract Cancer

Intervention

Nivolumab

Study Arms / Comparison Groups

 DKN 01 and Nivolumab Safety Run in
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

October 7, 2019

Completion Date

August 31, 2024

Primary Completion Date

August 31, 2022

Eligibility Criteria

        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
             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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Lipika Goyal, MD, 617-724-4000, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04057365

Organization ID

19-200


Responsible Party

Principal Investigator

Study Sponsor

Massachusetts General Hospital

Collaborators

 Bristol-Myers Squibb

Study Sponsor

Lipika Goyal, MD, Principal Investigator, Massachusetts General Hospital


Verification Date

January 2021