Trametinib in Combination With Sorafenib in Patients With Advanced Hepatocellular Cancer

NCT02292173 | Completed Phase 1 FDA Drug

• 1 other identifier: MCC-17932
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to see whether the combination of trametinib and sorafenib can help people with hepatocellular cancer. Researchers also want to find out if the combination of trametinib and sorafenib is safe and tolerable.

Conditions

Hepatocellular Cancer; Liver Cancer

Keywords

Liver Neoplasms; Liver Diseases; Digestive System Diseases; Advanced; Mitogen-Activated Protein Kinase (MEK) Inhibitor; Kinase Inhibitor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The MTD for study is defined as the highest dose level at which 1 or less of 6 patients experience a dose limiting toxicity (DLT).

  Up to 18 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Up to 3 years

• Response Rate

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

Study Arms (1)

Trametinib plus Sorafenib

EXPERIMENTAL

Dose Escalation Followed by Dose Expansion. Trametinib: Daily (To start on day 8 during cycle 1 and on day 1 from cycle 2 onwards), according to dose level upon entry. Sorafenib: Twice daily, according to dose level upon entry. Each cycle is repeated every 28 days.

Drug: Trametinib; Drug: Sorafenib

Interventions

Trametinib DRUG

Dose Escalation: Level 1: 1 mg daily. Level 2: 1.5 mg daily. Level 3: 1.5 mg daily. Level 4: 2 mg daily. Dose Expansion: Maximum Tolerated Dose (MTD)

Also known as: MEKINIST®

Trametinib plus Sorafenib

Sorafenib DRUG

Dose Escalation: Level 1: 200 mg twice daily. Level 2: 200 mg twice daily. Level 3: 400 mg twice daily. Level 4: 400 mg twice daily. Dose Expansion: Maximum Tolerated Dose (MTD)

Also known as: Nexavar®

Trametinib plus Sorafenib

Eligibility Criteria

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

You may qualify if:

• Must have radiographic or histological diagnosis of hepatocellular cancer (HCC), with advanced stage disease that is not amenable to curative surgical resection. Potential participants without histologic diagnosis must meet the radiographic criteria for HCC.
• Child Pugh score must be 5 or 6 (Child Pugh Class A)
• Must have measurable disease by RECIST criteria 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Must have normal organ and marrow function
• Female participants of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for four months following the last dose.
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Participants in the dose expansion part must have tumor that is amenable for biopsy.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Have received radiation therapy, major surgery, other locoregional therapy, within 4 weeks prior to the first dose of study drug
• All prior treatment-related toxicities must be ≤ Grade 1.
• Have received sorafenib or other systemic therapies for treatment of HCC in the past
• Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures
• History or evidence of cardiovascular risk
• Known history of human immunodeficiency virus (HIV) positivity
• History of retinal vein occlusion (RVO)
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
• History of interstitial lung disease or pneumonitis
• Are pregnant or lactating
• Any underlying condition that would significantly interfere with the absorption of an oral medication
• History of another active malignancy in last 3 years. Exception: Potential participants who have been disease-free for 3 years, or have a history of completely resected nonmelanoma skin cancer and/or potential participants with indolent second malignancies are eligible.
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide
• Concurrent therapy with approved or investigational anticancer therapy

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Kim R, Tan E, Wang E, Mahipal A, Chen DT, Cao B, Masawi F, Machado C, Yu J, Kim DW. A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer. Oncologist. 2020 Dec;25(12):e1893-e1899. doi: 10.1634/theoncologist.2020-0759. Epub 2020 Sep 14.

  PMID: 32776632 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Liver Diseases; Digestive System Diseases

Interventions

trametinib; Sorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms

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

• Richard Kim, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: November 17, 2014
• Study Start: February 18, 2015
• Primary Completion: December 18, 2018
• Study Completion: January 1, 2021
• Last Updated: June 10, 2021

Record last verified: 2021-01

Locations

US (1)