- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03501368
Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma
February 26, 2024 updated by: H. Lee Moffitt Cancer Center and Research Institute
Phase 1 Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma
The main purpose of this study is to determine the risks and benefits of ceritinib (ZYKADIA) given in combination with trametinib (MEKINIST) in patients who have progressed on prior melanoma therapy.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
Ceritinib that has been approved for patients with metastatic non-small cell lung cancer (NSCLC) by the US Food and Drug Administration (FDA).
While ceritinib is not currently FDA-approved specifically in melanoma, researchers believe ceritinib may also help keep melanoma cancer cells from growing and therefore potentially help patients with melanoma as well.
Trametinib is currently FDA-approved for melanoma with a BRAFV600-mutation.
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Diagnosis of advanced/unresectable melanoma (AJCC v.8 Stage 3C/D/4)
- Measurable disease, defined as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Must have at least one tumor site accessible for a biopsy
- Documented disease refractory to at least one PD1/PD-L1 (+/- CTLA-4) inhibitor treatment, or intolerance to these drugs and if BRAFV600-mutant melanoma, refractory disease to at least one BRAF and MEK inhibitor (defined as progression while on treatment), or intolerance to these drugs
- Last line of treatment prior to study enrollment must not have been BRAF/MEK inhibitor therapy
- Prior treatment-related toxicity resolved to ≤ Grade 2 or baseline
- Prior radiation allowed
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 90 days after completion of trametinib + ceritinib administration.
- Participants must have normal organ and marrow function.
Exclusion Criteria:
- Potential participants with known hypersensitivity to any of the excipients of trametinib, ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
- An untreated or uncontrolled brain metastases or evidence of leptomeningeal disease. Patients with asymptomatic brain metastases or previously treated brain metastases that are stable (i.e., not requiring corticosteroids) at the time of study start will be eligible.
- Previous malignancy is not an exclusion provided that the other malignancy is considered under control, patient is not on concomitant anti-cancer drug therapy, and target lesions from melanoma are clearly defined for response assessment.
- Other severe, acute, or chronic medical conditions including uncontrolled diabetes mellitus or psychiatric conditions or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results.
Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
- unstable angina within 6 months prior to screening;
- myocardial infarction within 6 months prior to screening;
- history of documented congestive heart failure (New York Heart Association functional classification III-IV);
- cardiac arrhythmias not controlled with medication;
- Corrected QT (QTcF) >470 ms at baseline
- A history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention). (Note, this does NOT include immune-mediated pneumonitis)
- Impaired gastrointestinal (GI) function or GI disease that may alter absorption of study drugs or inability to swallow
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to start of treatment with study drugs and for the duration of participation:
- Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes
- Strong inhibitors or strong inducers of CYP3A4/5, and Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, and/or CYP2C9
- Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban).
- Unstable or increasing doses of corticosteroids in the 5 days before first dose of study treatment.
- Enzyme-inducing anticonvulsive agents
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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 + Ceritinib Treatment
Study treatment will be given in cycles.
Each cycle will be 4 weeks (28 days).
Post-Treatment (follow-up) Period: Participants will return to the study site between 30-40 days after the last dose of trametinib + ceritinib for an end-of-treatment assessment.
Additional follow-up will occur for related Adverse Events (AEs) that are not resolved by this time and related Serious Adverse Events (SAEs) that occur after the time of this visit.
Participants will be followed for survival every 3 months for the first year following end of treatment, and then every 6 months for up to 5 years after end of treatment.
|
Participants will take ceritinib by mouth (PO) once daily at a dose of up to 450 mg (3 capsules of 150 mg)
Other Names:
Participants will take trametinib by mouth at a dose of 2 mg daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) and recommended Phase 2 Dose (RP2D)
Time Frame: Up to 12 months
|
Maximum Tolerated Dose and recommended phase 2 dose of trametinib + ceritinib, determined by number and frequency of treatment related adverse events
|
Up to 12 months
|
Overall Response Rate (ORR)
Time Frame: Up to 6 months post treatment
|
ORR will be defined by proportion of patients who have achieved a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Complete Response (CR): Disappearance of all target lesions.
Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
|
Up to 6 months post treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Progression-free Survival (PFS)
Time Frame: Up to 5 years post treatment
|
PFS is defined from the time of on-treatment to time of progression, censoring at last clinical follow up or if no longer followed at Moffitt, then based on date of last medical documentation of no progression.
Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
|
Up to 5 years post treatment
|
Overall Survival (OS)
Time Frame: Up to 5 years post treatment
|
OS is defined as from the time of on-treatment to the time of death, censoring at last date known alive.
|
Up to 5 years post treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Zeynep Eroglu, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 27, 2018
Primary Completion (Actual)
October 28, 2022
Study Completion (Estimated)
March 1, 2024
Study Registration Dates
First Submitted
April 10, 2018
First Submitted That Met QC Criteria
April 16, 2018
First Posted (Actual)
April 18, 2018
Study Record Updates
Last Update Posted (Estimated)
February 28, 2024
Last Update Submitted That Met QC Criteria
February 26, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Trametinib
- Ceritinib
Other Study ID Numbers
- MCC-19475
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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 Melanoma
-
H. Lee Moffitt Cancer Center and Research InstituteTurnstone Biologics, Corp.RecruitingMetastatic Melanoma | Conjunctival Melanoma | Ocular Melanoma | Unresectable Melanoma | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Iris Melanoma | Acral Melanoma | Non-Cutaneous MelanomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IA Melanoma | Stage IB Melanoma | Stage IIA MelanomaUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
-
MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
-
National Cancer Institute (NCI)CompletedStage IV Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Iris Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIB Melanoma | Stage IIC MelanomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
-
Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
Clinical Trials on Ceritinib
-
Novartis PharmaceuticalsAvailableNon-small Cell Lung Cancer (NSCLC) | Anaplastic Lymphoma Kinase (ALK)- Positive Tumors
-
Novartis PharmaceuticalsCompletedNon-Small Cell Lung CancerCanada, Taiwan, United States, Italy, Korea, Republic of, Thailand, Belgium, Germany, Austria, Turkey, Greece, United Kingdom, Colombia, India, Malaysia, Brazil, Spain, Poland, Bulgaria, Australia, Czechia, Lebanon, Netherlands, Russian...
-
Novartis PharmaceuticalsTerminatedGlioblastoma | Anaplastic Large Cell Lymphoma | Inflammatory Myofibroblastic Tumor | Tumors With Aberrations in ALKFrance, Czechia, Italy, Spain, Korea, Republic of, Thailand, Israel, Denmark
-
St. Joseph's Hospital and Medical Center, PhoenixNovartis; Wayne State University; Translational Genomics Research InstituteCompletedGlioblastoma | Brain MetastasesUnited States
-
Yonsei UniversityUnknownNon-small Cell Lung Cancer Harboring ROS1 RearrangementKorea, Republic of
-
Novartis PharmaceuticalsRecruitingALK Positive MalignanciesGermany, France, Australia, Belgium, Italy, Korea, Republic of, Poland, China, United States, Taiwan, Brazil, Bulgaria, Hong Kong, Japan, Lebanon, Malaysia, Spain, Russian Federation, Colombia, Singapore, Czechia
-
Anne Beaven, MDNovartisWithdrawnHematologic MalignanciesUnited States
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; National Cheng-Kung University HospitalTerminated
-
Criterium, Inc.University of Colorado, Denver; NovartisTerminatedPancreatic Adenocarcinoma | Gastric Adenocarcinoma | Cholangiocarcinoma | Esophageal Adenocarcinoma | Colorectal Adenocarcinoma | Hepatocellular AdenocarcinomaUnited States
-
Novartis PharmaceuticalsActive, not recruitingALK-positive NSCLCBelgium, Spain, Italy, Australia, United States, Hong Kong, Canada, Singapore