Study of Enzalutamide With and Without Sorafenib in Advanced Hepatocellular Carcinoma Patients

NCT02642913 | Completed Phase 1

• 1 other identifier: 15-279
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to test the safety of enzalutamide with or without sorafenib at different doses. Enzalutamide is approved by the Food and Drug Administration (FDA) for the treatment of advanced prostate cancer. Enzalutamide blocks a protein called the androgen receptor. Experiments on liver cancer cells and animal models show that blocking the androgen receptor causes liver cancer to stop growing. Enzalutamide has not been approved to treat liver cancer. The investigators want to see if enzalutamide is safe for patients with liver cancer who have had their tumors grow on sorafenib. The investigators also want to see how safe and effective sorafenib and enzalutamide are for liver cancer patients that have never been treated with sorafenib. This is the first time enzalutamide and sorafenib are being used together. This treatment may not help treat the participant's cancer.

Conditions

Hepatocellular Carcinoma

Keywords

Enzalutamide; Sorafenib; 15-279

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  survival is defined as the time from the initiation of study treatment to HCC radiographic progression or death. Four month PFS is defined as the proportion of patients alive and progression free at 4 months. Patients that come out of study before evaluation of the 4 month endpoint without documented progression will be considered as events for the primary endpoint of 4 month PFS. Progression will be by RECIST 1.1.

  4 months

Study Arms (2)

Enzalutamide without Sorafenib

EXPERIMENTAL

Will get enzalutamide, at the dose approved by the FDA for prostate cancer. If this dose has serious side effects, a lower dose will be given to new patients as they take part in the study. At the end of this part of the study, the recommended dose of enzalutamide will be set for all patients on this study. More patients will then be treated with this dose.

Drug: Enzalutamide

Enzalutamide with Sorafenib

EXPERIMENTAL

Will get enzalutamide and sorafenib. The first group of patients will get the recommended dose of enzalutamide with sorafenib by mouth either once or twice daily. The dose of sorafenib you receive will depend on when the patient starts the study. At the beginning of the study, patients will be treated with a lower dose of sorafenib. If this dose does not have serious side effects, a higher dose will be given to new patients as they take part in the study.

Drug: Enzalutamide; Drug: Enzalutamide with Sorafenib

Interventions

Enzalutamide DRUG

Enzalutamide with Sorafenib; Enzalutamide without Sorafenib

Enzalutamide with Sorafenib DRUG

Enzalutamide with Sorafenib

Eligibility Criteria

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

You may qualify if:

• Histologic proof of HCC reviewed and confirmed at per the local standard of care.
• Advanced unresectable or metastatic disease
• Measurable disease as defined by RECIST version 1.1
• Tissue available for the evaluation of AR by IHC on pretreatment HCC samples. If tissue is not available, a pretreatment biopsy will not be necessary for eligibility
• Age ≥ 18 years-old
• ECOG performance status ≤ 2
• Child-Pugh category A
• Adequate hepatic function defined by:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5.0 x upper limit of normal (ULN)
• Total Bilirubin ≤ 1.5 x ULN
• Adequate hematologic function defined by:
• Absolute neutrophil count (ANC) ≥ 1200/mm3 (≥ 1.2 x 10\^9/L)
• Platelets ≥ 75,000/mm3 (≥ 75 x 10\^9/L)
• Hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Adequate renal function defined by:

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• For patients who will receive enzalutamide monotherapy, failure or intolerance of prior sorafenib is required for enrollment. For patients who will receive combination therapy, prior sorafenib is excluded.
• Patients may not have received cytotoxic, biologic or small molecule kinase inhibitor systemic therapy f or at least 3 weeks prior to the first dose of study treatment.
• Patients must not have received prior regional therapy such as ablation, embolization, or radiation therapy for at least 2 weeks prior to the first dose of study treatment. Patients who receive such therapy should have evidence of radiologic progression at this site or other progressing measurable disease.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before study enrollment. Eligible subjects must be without corticosteroid treatment at the time of study enrollment.
• History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months of enrollment.
• Clinically significant cardiovascular disease including:
• Myocardial infarction within six months prior to Screening;
• Uncontrolled angina within three months prior to Screening;
• Congestive heart failure NYHA class 3 or 4, or subjects with history of congestive heart
• failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or MUGA scan
• performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%;
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
• Anticoagulation with warfarin

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Astellas Pharma US, Inc.: collaborator
• Mayo Clinic: collaborator
• University of California, San Francisco: collaborator
• University of Southern California: collaborator
• Washington University School of Medicine: collaborator
• Roswell Park Cancer Institute: collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

enzalutamide; Sorafenib

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)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• James Harding, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2015
• First Posted: December 30, 2015
• Study Start: December 1, 2015
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: March 5, 2021

Record last verified: 2021-03

Locations

US (5)