Clinical Trials /

A Phase II, Randomized, Controlled Trial of Nivolumab in Combination With BMS-986253 or Cabiralizumab in Advanced Hepatocellular Carcinoma (HCC) Patients

NCT04050462

Description:

A phase II clinical trial is utilized to examine whether BMS-986253 (25 subjects) or Cabiralizumab (25 subjects) when combined with Nivolumab offers improved radiographic objective response rates (ORR) over Nivolumab monotherapy (25 subjects) in advanced HCC patients.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II, Randomized, Controlled Trial of Nivolumab in Combination With BMS-986253 or Cabiralizumab in Advanced Hepatocellular Carcinoma (HCC) Patients
  • Official Title: A Phase II, Randomized Controlled Trial of Nivolumab in Combination With BMS-986253 or Cabiralizumab in Advanced Hepatocellular Carcinoma (HCC)

Clinical Trial IDs

  • ORG STUDY ID: 18-01028
  • NCT ID: NCT04050462

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
Nivolumab 240 mg IV every 2 weeks + Cabiralizumab 4 mg/kg IV every 2 weeksNivolumab/Cabiralizumab combination
Nivolumab 240 mg IV every 2 weeks + BMS-986253 1200 mg IV every 2 weeksNivolumab/BMS-986253 combination
Nivolumab 240 mg IV every 2 weeksNivolumab Monotherapy

Purpose

A phase II clinical trial is utilized to examine whether BMS-986253 (25 subjects) or Cabiralizumab (25 subjects) when combined with Nivolumab offers improved radiographic objective response rates (ORR) over Nivolumab monotherapy (25 subjects) in advanced HCC patients.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab MonotherapyActive Comparator
  • Nivolumab 240 mg IV every 2 weeks
Nivolumab/BMS-986253 combinationExperimental
  • Nivolumab 240 mg IV every 2 weeks + BMS-986253 1200 mg IV every 2 weeks
  • Nivolumab 240 mg IV every 2 weeks
Nivolumab/Cabiralizumab combinationExperimental
  • Nivolumab 240 mg IV every 2 weeks + Cabiralizumab 4 mg/kg IV every 2 weeks
  • Nivolumab 240 mg IV every 2 weeks

Eligibility Criteria

        Inclusion Criteria:

          1. Have histologically confirmed evidence of HCC, Childs-Pugh score of ≤7.

             a. Participants must be willing to provide specimen from fresh, pre- and on-treatment
             tumor core biopsies for histologic diagnosis and translational studies.

          2. Radiographically measurable disease by RECIST1.1 in at least one site.

          3. Deemed to not be a candidate for resection or other local-regional therapy.

          4. Must not be receiving treatment with other investigational agents and must not have
             received any other systemic therapy prior to registration.

             a. Prior radioembolization, local ablative therapies (radiofrequency, microwave or
             cryoablation), radiation (external beam or stereotactic), or hepatic resection
             permitted if completed ≥ 4 weeks prior to study enrollment and if patient has
             recovered with ≤ grade 1 toxicity and if untreated measurable disease is present.

          5. Be willing and able to provide written informed consent/assent for the trial.

          6. Participants must be ≥ 18 years

          7. Have a Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          8. If hepatitis B is present, participants must be on anti-viral HBV therapy.

          9. All women of childbearing potential (not surgically sterilized and between menarche
             and 1 year post menopause) must have a blood test to rule out pregnancy within 24
             hours prior to start of study treatment

         10. All women of childbearing potential must agree to follow instructions for method(s) of
             contraception for the duration of treatment with study treatment (s) and for 5 months
             following discontinuation of study treatment.

         11. Males who are sexually active with women of childbearing potential must agree to
             follow instructions for method (s) of contraception for the duration of treatment with
             study treatment and for 7 months following discontinuation of study treatment.
             Additionally, male participants must not donate sperm during this period.

         12. Demonstrate adequate organ function as defined by the following required lab and
             acceptable range criteria:

        Adequate bone marrow function:

        Absolute neutrophil count > 1000/mcL Platelet count > 50,000/mcL Hemoglobin > 8.5 g/dL

        Adequate hepatic function:

        Total bilirubin < 2 mg/dL or < 1.5 times upper limit of normal (ULN) AST and ALT < 5 times
        ULN INR < 1.5 times ULN Albumin > 2.8 g/dL

        Adequate renal function:

        Creatinine < 2.0 mg/Dl

        Exclusion Criteria:

          1. Women who are pregnant or breastfeeding.

          2. Presence of other malignancies. Participants with active second malignancy other than
             non-melanoma skin cancer or cervical carcinoma in situ. NOTE: Patients with history of
             malignancy are not considered to have a "currently active" malignancy if they have
             completed therapy and are now considered by their physician to be at less than 30%
             risk for relapse.

          3. Have active or history of Tuberculosis

          4. Participants with known HIV positive status

          5. Participants with known CNS metastases

          6. Uncontrolled ascites

          7. Uncontrolled encephalopathy

          8. Uncontrolled gastro-esophageal varicesPrior organ allograft or allogeneic bone marrow
             transplantation

          9. Participants with active, known, or suspected autoimmune disease. Participants with
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition only requiring hormone replacement, euthyroid participants with a history of
             Grave's disease (participants with suspected autoimmune thyroid disorders must be
             negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating
             immunoglobulin prior to first dose of study treatment), psoriasis not requiring
             systemic treatment, or conditions not expected to recur in the absence of an external
             trigger are permitted to enroll.

         10. Participants with a condition requiring systemic treatment with either corticosteroids
             (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
             14 days of study treatment administration except for adrenal replacement steroid doses
             > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note:
             Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating
             study treatment is permitted.

         11. Interstitial lung disease that is symptomatic or may interfere with the detection or
             management of suspected treatment-related pulmonary toxicity.

         12. Uncontrolled or significant cardiovascular disease including, but not limited to, any
             of the following:

               -  Myocardial infarction or stroke/transient ischemic attack within the past 6
                  months

               -  Uncontrolled angina within the past 3 months

               -  Any history of clinically significant arrhythmias (such as ventricular
                  tachycardia, ventricular fibrillation, or torsades de pointes)

               -  History of other clinically significant heart disease (eg, cardiomyopathy,
                  congestive heart failure with New York Heart Association functional
                  classification III to IV, pericarditis, significant pericardial effusion, or
                  myocarditis)

               -  Cardiovascular disease-related requirement for daily supplemental oxygen therapy.

         13. Participants with ongoing or active, uncontrolled infections (afebrile for ≥ 48 hours
             off antibiotics). If hepatitis B is present, must be on anti-viral HBV therapy.

         14. 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.

         15. Any major surgery within 4 weeks of study treatment. Participants must have recovered
             from the effects of major surgery or significant traumatic injury at least 14 days
             before

         16. Any uncontrolled inflammatory disease including Crohn's disease and ulcerative colitis

         17. Treatment with botanical preparations (eg, herbal supplements, including potential
             drugs of abuse, or traditional Chinese medicines) intended for general health support
             or to treat the disease under study within 2 weeks prior to randomization/treatment.

         18. Concomitant use of statins while on study.

         19. Current or history of clinically significant muscle disorders (eg, myositis), recent
             unresolved muscle injury, or any condition known to elevate serum CK levels.

         20. Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and
             Tween 80 (polysorbate 80).

         21. Participants who have received a live / attenuated vaccine within 30 days of first
             treatment.

         22. Concomitant use of any live / attenuated vaccine during treatment and until 100 days
             following last dose.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) of Cabiralizumab or BMS-986253 in combination with Nivolumab in comparison to Nivolumab monotherapy
Time Frame:6 Years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NYU Langone Health

Last Updated

August 5, 2020