- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02292173
Trametinib in Combination With Sorafenib in Patients With Advanced Hepatocellular Cancer
A Phase 1a/1b Trial of Trametinib in Combination With Sorafenib in Patients With Advanced Hepatocellular Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
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)
Other Names:
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)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: Up to 18 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: Up to 3 years
|
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).
|
Up to 3 years
|
Response Rate
Time Frame: Up to 3 years
|
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.
|
Up to 3 years
|
Overall Survival (OS)
Time Frame: Up to 3 years
|
Overall Survival is defined as the time period from start of treatment to death.
|
Up to 3 years
|
Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Carcinoma, Hepatocellular
- Liver Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Sorafenib
- Trametinib
Other Study ID Numbers
- MCC-17932
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Liver Cancer
-
Slawa CwajnaNova Scotia Health AuthorityWithdrawnPrimary Liver Cancer | Metastatic Liver CancerCanada
-
Duke UniversityCompletedPrimary Liver Cancer | Metastatic Liver Cancer From Any Cancer SiteUnited States
-
University of HawaiiGlaxoSmithKlineRecruitingAdvanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Adult Primary Liver CancerUnited States
-
Célia TurcoCompletedPrimary Liver Cancer | Liver Metastases | Secondary Liver CancerFrance
-
University of CincinnatiActive, not recruitingLiver Metastases | Advanced Adult Primary Liver Cancer | Localized Unresectable Adult Primary Liver Cancer | Recurrent Adult Primary Liver CancerUnited States
-
Lisa H. Butterfield, Ph.D.National Cancer Institute (NCI)TerminatedHepatocellular Carcinoma | Liver Cancer | Cancer of Liver | Hepatoma | Hepatocellular Cancer | Hepatic Cancer | Liver Cell Carcinoma | Cancer, Hepatocellular | Liver Cancer, Adult | Liver Cell Carcinoma, Adult | Cancer of the Liver | Neoplasms, Liver | Hepatic Neoplasms | Neoplasms, HepaticUnited States
-
Radboud University Medical CenterTerumo Medical CorporationCompletedPrimary Liver Cancer | Liver Cancer | Liver Metastasis Colon CancerNetherlands
-
Cardiovascular and Interventional Radiological...RecruitingPrimary Liver Cancer | Secondary Liver CancerGermany
-
Shanghai Huihe Medical Technology Co., LtdEnrolling by invitation
-
Burzynski Research InstituteTerminatedPrimary Liver CancerUnited States
Clinical Trials on Trametinib
-
Melanoma Institute AustraliaNovartisRecruiting
-
Memorial Sloan Kettering Cancer CenterCompletedNon Small Cell Lung Cancer | KRAS Gene MutationUnited States
-
GlaxoSmithKlineCompleted
-
GlaxoSmithKlineCompleted
-
Stanford UniversityBoston Children's HospitalRecruitingArterial Disease | Venous MalformationUnited States
-
The Netherlands Cancer InstituteGlaxoSmithKlineUnknown
-
University Health Network, TorontoNot yet recruitingArteriovenous Malformations
-
Shanghai Henlius BiotechRecruiting
-
Dana-Farber Cancer InstituteNovartis; National Comprehensive Cancer NetworkTerminated
-
Universitair Ziekenhuis BrusselCompleted