Clinical Trial: Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That Is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Non-randomized, Open-Label, Phase 2 Study of Trametinib in Patients With Unresectable or Metastatic Epithelioid Hemangioendothelioma

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

Detailed Summary:

PRIMARY OBJECTIVES:

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.

TERTIARY 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. Courses repeat every 28 days for up to 52 courses in the absence of disease progression or unacceptable toxicity.

A Simon minimax sampling two-stage design will be used to estimate the objective response rate. Will be calculated along with 95% confidence intervals.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in patient reported symptoms as assessed by National Institutes of Health Patient Reported Outcomes Measurement Information System questionnaire [ Time Frame: Baseline up to 6 months ]
    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.
  • Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 4.0 [ Time Frame: Up to 6 months ]
    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.
  • Median progression-free survival [ Time Frame: From time of first dose of study medication to occurrence of radiologic tumor progression per Response Evaluation Criteria in Solid Tumors 1.1, clinical progression based on treating physician assessment or death from any cause, assessed up to 6 months ]
    Will be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.
  • Overall survival [ Time Frame: From the time of first dose of study drug to occurrence of death from any cause, assessed at 2 years ]
    Will be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.
  • Progression-free survival [ Time Frame: From time of first dose of study medication to occurrence of radiologic tumor progression per Response Evaluation Criteria in Solid Tumors 1.1, clinical progression based on treating physician assessment or death from any cause, assessed at 6 months ]
    Will be calculated along with 95% confidence intervals and estimated by the Kaplan-Meier method.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 1, 2017
Date Started: April 19, 2017
Date Completion: December 31, 2023
Last Updated: May 9, 2017
Last Verified: May 2017