Neoplasms

All Conditions

Rare Diseases

Hemangioendothelioma

Hemangioendothelioma, Epithelioid

Hemangioma

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Trametinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.

Questionnaire Administration

Scott M Schuetze

This phase II trial studies how well trametinib works in treating patients with epithelioid hemangioendothelioma that has spread to other places in the body (metastatic), nearby tissue or lymph nodes (locally advanced), or cannot be removed by surgery (unresectable). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. Estimate the objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

SECONDARY OBJECTIVES:

I. Estimate the 6-month and median progression free survival (PFS) rates. II. Estimate the 2-year and median overall survival (OS) rates. III. Evaluate the safety of trametinib in patients with epithelioid hemangioendothelioma.

IV. Evaluate patient-reported symptoms using National Institutes of Health Patient Reported Outcomes Measurement Information System (NIH PROMIS) global health; pain intensity, interference and behavior short form inventories prior to, after 4 weeks and after 6 months (if stable or better disease) of treatment, and on evidence of disease progression.

EXPLORATORY OBJECTIVES:

I. Compare the rates of epithelioid hemangioendothelioma progression prior to starting trametinib to rates on treatment by central review of radiology images.

II. Evaluate the effect of trametinib on change in tumor volume and compare to RECIST 1.1 response through central imaging review.

III. Evaluate the effect of trametinib on markers of inflammation including c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and plasma connective tissue growth factor (CTGF).

OUTLINE:

Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 52 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 6 months.

Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery

A Non-Randomized, Open-Label, Phase 2 Study of Trametinib in Patients With Unresectable or Metastatic Epithelioid Hemangioendothelioma

McNemar test will be used to compare the number of patients with epithelioid hemangioendothelioma progression prior to starting trametinib to the number of patients with epithelioid hemangioendothelioma progression during treatment.

Will be used as time-dependent variables in a Cox model to determine the association with epithelioid hemangioendothelioma survival.

Will be analyzed by enzyme-linked immunosorbent assay. Will be used as time-dependent variables in a Cox model to determine the association with epithelioid hemangioendothelioma survival.

Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be summarized with a scatterplot. The Pearson correlation coefficient (or Spearman, if more appropriate) will be assessed to determine the strength of the agreement. Agreement of the tumor classifications (response versus no response) will be summarized as the raw agreement and with a Kappa Statistic. The association of the change in tumor volume with survival will be evaluated in two ways. The first will be to use the change in tumor volume as a time dependent variable in a Cox model. The second will be a landmark analysis (done at either the first radiographic assessment or at the second radiographic assessment) to compare the survival of patients classified as a responder (based on tumor volume) to those who have not responded by the selected landmark time. Patients who died prior to the landmark time point will be omitted from analysis.

Will be evaluated by fluorescence in situ hybridization.

Will be analyzed by immunohistochemistry. Descriptive statistics will be generated, and estimates for the proportion of samples with demonstrated inhibition of MAPK signaling post-treatment compared to pre-treatment will be generated along with 95% confidence intervals. Likewise, the proportion of patients with demonstrated MAPK signaling inhibition at time of disease progression will be determined with the corresponding 95% confidence interval.

Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. A Simon minimax sampling two-stage design will be used to estimate the objective response rate. Will be calculated along with 95% confidence intervals.

Will be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.

Graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. The rates of adverse events occurring in at least 5% of subjects and rates of grade 3-5 adverse events will be tabulated by system and term.

Will be assessed by the National Institutes of Health Patient Reported Outcomes Measurement Information System questionnaire. Patient Reported Outcomes Measurement Information System questionnaires will be scored according to recommended standardized system and t-scores generated. A mixed model will be used to analyze change in t-scores over time.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery	NCT03148275	Locally Advance... Metastatic Epit... Unresectable Ep...	Questionnaire A... Trametinib	15 Years -	National Cancer Institute (NCI)
Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery	NCT03148275	Locally Advance... Metastatic Epit... Unresectable Ep...	Questionnaire A... Trametinib	15 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for unresectable epithelioid hemangioendothelioma