Abemaciclib and Nivolumab for Subjects With Hepatocellular Carcinoma

NCT03781960 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: UPCC 35218
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  up to 2 years

Secondary Outcomes (3)

• Progression-Free Survival

  From the start of study treatment until disease progression, death, whichever came first up to 2 years

• Duration of Response

  up to 2 years

• Overall Survival

  From the start of treatment to death, due to any cause or last patient contact alive, assessed up to 2 years

Study Arms (1)

Abemaciclib & Nivolumab

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

Abemaciclib DRUG

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

Also known as: Verzenio

Abemaciclib & Nivolumab

Nivolumab 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.

Also known as: Opdivo

Abemaciclib & Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have hepatocellular carcinoma (HCC) that is inoperable (where surgery is not indicated due to disease extent, co-morbidities, or other technical reasons)
• 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.
• Tumor must be positive for retinoblastoma (RB) expression by immunohistochemistry
• Age \> 18 years and ability to understand and the willingness to sign a written informed consent document.
• ECOG performance status of 0 or 1
• Childs-Pugh score of \<7
• Life expectancy of at least 12 weeks
• Must be able to swallow tablets
• Must be willing to comply with protocol procedures (including completion of diaries and outcome measures)
• 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
• Must be willing to undergo a pretreatment and on-treatment biopsy and have a tumor site that is accessible for core needle biopsy
• Measurable or evaluable disease as defined by RECIST v. 1.1
• 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.
• Subjects with hepatitis B must have an HBV viral load \< 100 IU/mL by PCR during screening
• Must have adequate organ and hematopoietic function as defined below:

You may not qualify if:

• Any history of a serious medical or psychiatric condition that would prevent the subject from signing the informed consent form
• Pregnant or breastfeeding
• Use of any chemotherapy within 3 weeks prior to the first study treatment date
• Use of any experimental therapy within 4 weeks or 5 half-lives, whichever is longer, prior to the first study treatment date
• Use of radiation within 2 weeks prior to the first study treatment date (4 weeks if radiation to liver as per section 4.1)
• Prior treatment with a CDK 4/6 inhibitor
• Prior treatment with a PD-1 or PD-L1 inhibitor
• 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
• Subjects may not receive concomitant anticancer agents or radiation. Antiviral agents aimed at treating infectious hepatitis are permitted
• History of or suspected hypersensitivity to nivolumab or abemaciclib
• Uncontrolled ascites
• Esophageal varices requiring treatment within the past 6 months (banding or medication)
• 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.
• 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
• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

abemaciclib; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Thomas Karasic, MD
• Organization: University of Pennsylvania Hospital

thomas.karasic@pennmedicine.upenn.edu

215-614-1858

Study Officials

• Thomas Karasic, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 20, 2018
• Study Start: July 31, 2019
• Primary Completion: April 29, 2022
• Study Completion: April 29, 2022
• Last Updated: December 14, 2022
• Results First Posted: December 14, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)