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Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03781960
Recruitment Status : Not yet recruiting
First Posted : December 20, 2018
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Abemaciclib Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Abemaciclib
Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.

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.




Primary Outcome Measures :
  1. Overall response rate by investigator review [ Time Frame: Assessed at the completion of all subjects' participation on the study, estimated to be approximately 36 months ]
    Overall response rate by investigator review using RECIST v. 1.1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03781960


Contacts
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Contact: Thomas Karasic, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Thomas Karasic, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Sub-Investigator: Mark O'Hara, MD         
Sub-Investigator: Kim Reiss-Binder, MD         
Sub-Investigator: Ursina Teitelbaum, MD         
Sub-Investigator: Charles Schneider, MD         
Sub-Investigator: Jennifer Eads, MD         
Sub-Investigator: Nevena Damjanov, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
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Principal Investigator: Thomas Karasic, MD Abramson Cancer Center of the University of Pennsylvania

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Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03781960    
Other Study ID Numbers: UPCC 35218
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents