Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Abemaciclib; Nivolumab
Intervention description: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.; Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to evaluate the effectiveness of the combination of
      nivolumab and abemaciclib for the treatment of hepatocellular carcinoma. Other goals of this
      study are to learn about the side effects that this combination of drugs may cause and to
      learn more about how these drugs work by studying blood and tissue.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must have hepatocellular carcinoma (HCC) that is inoperable (where surgery is
             not indicated due to disease extent, co-morbidities, or other technical reasons)

          2. Histologic confirmation of HCC is not required for screening but is required prior to
             initiation of study treatment. Subjects with hepatocholangiocarcinoma or
             cholangiocarcinoma are not eligible.

          3. Tumor must be positive for retinoblastoma (RB) expression by immunohistochemistry

          4. Age > 18 years and ability to understand and the willingness to sign a written
             informed consent document.

          5. ECOG performance status of 0 or 1

          6. Childs-Pugh score of <7

          7. Life expectancy of at least 12 weeks

          8. Must be able to swallow tablets

          9. Must be willing to comply with protocol procedures (including completion of diaries
             and outcome measures)

         10. Local or loco-regional therapy to the liver (i.e. surgery, radiation therapy, hepatic
             arterial embolization, chemoembolization, radiofrequency ablation, percutaneous
             ethanol injection, or cryoablation) must have been completed > 4 weeks prior to
             enrollment

         11. Must be willing to undergo a pretreatment and on-treatment biopsy and have a tumor
             site that is accessible for core needle biopsy

         12. Measurable or evaluable disease as defined by RECIST v. 1.1

         13. Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days of the first dose of abemaciclib (see Appendix A for definition of
             childbearing potential). Female subjects of childbearing potential must use an
             approved contraceptive method (detailed in Appendix A) for the duration of the study
             and an additional 3 weeks after the final dose of abemaciclib.

         14. Subjects with hepatitis B must have an HBV viral load < 100 IU/mL by PCR during
             screening

         15. Must have adequate organ and hematopoietic function as defined below:

        Exclusion Criteria:

          1. Any history of a serious medical or psychiatric condition that would prevent the
             subject from signing the informed consent form

          2. Pregnant or breastfeeding

          3. Use of any chemotherapy within 3 weeks prior to the first study treatment date

          4. Use of any experimental therapy within 4 weeks or 5 half-lives, whichever is longer,
             prior to the first study treatment date

          5. Use of radiation within 2 weeks prior to the first study treatment date (4 weeks if
             radiation to liver as per section 4.1)

          6. Prior treatment with a CDK 4/6 inhibitor

          7. Prior treatment with a PD-1 or PD-L1 inhibitor

          8. Those who have not recovered from adverse events < Grade 1 from prior therapy, with
             the exceptions of alopecia of any grade or stable peripheral neuropathy < Grade 2

          9. Subjects may not receive concomitant anticancer agents or radiation. Antiviral agents
             aimed at treating infectious hepatitis are permitted

         10. History of or suspected hypersensitivity to nivolumab or abemaciclib

         11. Uncontrolled ascites

         12. Esophageal varices requiring treatment within the past 6 months (banding or
             medication)

         13. Subjects with uncontrolled brain metastases. Subjects with brain metastases must have
             stable neurological status following local therapy (surgery or radiation) for at least
             4 weeks prior to first study treatment and must be off of steroids related to the
             brain metastases.

         14. Any concurrent condition requiring the continued or anticipated use of systemic
             steroids beyond physiologic replacement dosing (excluding non-systemic inhaled,
             topical skin, nasal, and/or ophthalmic corticosteroids). All other systemic
             corticosteroids above physiologic replacement dosing must be discontinued at least 4
             weeks prior to first study treatment

         15. Active drug or alcohol use or dependence as documented in the chart that, in the
             opinion of the investigator, would interfere with adherence to study requirements

         16. Active bacterial or fungal infection requiring IV therapy at the start of protocol
             treatment

         17. A second primary malignancy that, in the judgment of the investigator, may affect the
             interpretation of results

         18. Any illness or condition that in the opinion of the investigator may affect the safety
             of the subject or the evaluation of any study endpoint (e.g. interstitial lung
             disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical
             resection involving the stomach or small bowel, or preexisting Crohn's disease or
             ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or
             higher diarrhea)

         19. Personal history of ventricular tachycardia, ventricular fibrillation, or sudden
             cardiac arrest

         20. Prior organ allograft or allogeneic bone marrow transplantation

         21. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
             the normal range with medication

         22. Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma,
             atopic dermatitis, or endocrinopathies manageable by hormone replacement; other
             autoimmune conditions may be allowable at the discretion of the Principal Investigator

         23. Any other conditions judged by the investigator that would limit the evaluation of the
             subject

         24. HIV positive by PCR