Trametinib in Combination With Sorafenib in Patients With Advanced Hepatocellular Cancer

NCT ID: NCT02292173

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-18
• Study Completion Date: 2021-01-31

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.

Detailed Description

Each cycle will last for 4 weeks. Sorafenib and trametinib will be administered orally on continuous basis. During the first cycle sorafenib will be started on day 1 and trametinib on day 8 to improve tolerance. Participants will get restaging scans every 2 cycles. Participants will continue to receive treatment if they have a stable disease or a better response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.

Conditions

Hepatocellular Cancer; Liver Cancer

Study Design

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

Study Groups

Trametinib plus Sorafenib

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.

Group Type: EXPERIMENTAL

Trametinib

Intervention Type: 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)

Sorafenib

Intervention Type: 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)

Interventions

Trametinib

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)

Intervention Type: DRUG

Sorafenib

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)

Intervention Type: DRUG

Other Intervention Names

MEKINIST®; Nexavar®

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Concomitant use of strong Cytochrome P450 3A4 (CYP3A4) inducers

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

Sponsors

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Kim, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32776632 (View on PubMed)

Other Identifiers

MCC-17932

Identifier Type: -

Identifier Source: org_study_id