Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma

NCT ID: NCT03781960

Last Updated: 2022-12-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-31
• Study Completion Date: 2022-04-29

Brief 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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Abemaciclib & Nivolumab

Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.

Nivolumab

Intervention Type: DRUG

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.

Interventions

Abemaciclib

Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.

Intervention Type: DRUG

Nivolumab

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 Type: DRUG

Other Intervention Names

Verzenio; Opdivo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Karasic, MD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

UPCC 35218

Identifier Type: -

Identifier Source: org_study_id