Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma

NCT03501368 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCC-19475
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma; Unresectable Melanoma; Advanced Melanoma

Keywords

cutaneous; refractory; melanoma; ceritinib

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) and recommended Phase 2 Dose (RP2D)

  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)

  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 Outcomes (2)

• Median Progression-free Survival (PFS)

  Up to 5 years post treatment

• Overall Survival (OS)

  Up to 5 years post treatment

Study Arms (1)

Trametinib + Ceritinib Treatment

EXPERIMENTAL

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.

Drug: Ceritinib; Drug: Trametinib

Interventions

Ceritinib DRUG

Participants will take ceritinib by mouth (PO) once daily at a dose of up to 450 mg (3 capsules of 150 mg)

Also known as: ZYKADIA

Trametinib + Ceritinib Treatment

Trametinib DRUG

Participants will take trametinib by mouth at a dose of 2 mg daily

Also known as: MEKINIST

Trametinib + Ceritinib Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

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

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Melanoma

Interventions

ceritinib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Zeynep Eroglu, 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: April 10, 2018
• First Posted: April 18, 2018
• Study Start: June 27, 2018
• Primary Completion: October 28, 2022
• Study Completion: December 30, 2024
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)