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AzTrials

Hepatocellular CancerPhase 1NCT02292173

Trametinib in Combination With Sorafenib in Patients With Advanced Hepatocellular Cancer

A Phase 1 study testing Trametinib and Sorafenib in people with Hepatocellular Cancer and Liver Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Cancer, Liver Cancer
What is being tested?
Trametinib and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
18 Feb 2015to Jan 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 1a/1b Trial of Trametinib in Combination With Sorafenib in Patients With Advanced Hepatocellular Cancer

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.

Read the 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.

Being tested
Trametinib, Sorafenib
Keywords
Liver Neoplasms, Liver Diseases, Digestive System Diseases, Advanced, Mitogen-Activated Protein Kinase (MEK) Inhibitor, Kinase Inhibitor
Medical subject headings
Liver Neoplasms, Liver Diseases, Digestive System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrametinibDrug

    Also called MEKINIST®

    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)

  • SorafenibDrug

    Also called Nexavar®

    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)

Study groups in NCT02292173
Study groupRoleWhat they receive
Trametinib plus SorafenibExperimentalDose 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.
Receives: Drug: Trametinib; Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to 18 months

Secondary outcomes (3)

  1. Progression Free Survival (PFS)

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Further, modified RECIST criteria for HCC will be used to evaluate response. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Measured: Up to 3 years

  2. Response Rate

    Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Further, modified RECIST criteria for HCC will be used to evaluate response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Up to 3 years

  3. Overall Survival (OS)

    Overall Survival is defined as the time period from start of treatment to death.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2014 (estimated)
  2. Study start18 Feb 2015
  3. Primary completion18 Dec 2018
  4. Study completionJan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02292173
Sponsor's protocol ID
MCC-17932
Status last verified
Jan 2021
First submitted
12 Nov 2014
Last updated
10 Jun 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 32776632

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trametinib and Sorafenib in people with Hepatocellular Cancer and Liver Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02292173, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.

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