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

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Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; baseline imaging must be obtained within 30 days of day 1 of study
  • Patients must have histologically confirmed epithelioid hemangioendothelioma which is metastatic or locally advanced (unresectable)
  • Patients must have evidence of disease progression per RECIST 1.1 prior to enrollment or have evidence of cancer-related pain requiring symptom management with narcotic analgesics
  • Patients previously untreated or treated with drug therapy for epithelioid hemangioendothelioma (EHE) are eligible; there is no limit on the number of prior regimens used to be eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 6 months
  • Able to swallow 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 small bowel
  • All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade =< 1 (except alopecia) at the time of enrollment
  • Absolute neutrophil count (ANC) >= 1 x 10^9/L within 30 days of day 1 of study
  • Hemoglobin >= 9 g/dL, patients may receive transfusion to meet criterion within 30 days of day 1 of study
  • Platelets >= 75 x 10^9/L within 30 days of day 1 of study
  • Albumin >= 2.5 g/dL within 30 days of day 1 of study
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) within 30 days of day 1 of study; NOTE: patients with elevated bilirubin secondary to Gilbert’s disease are eligible to participate in the study
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN within 30 days of day 1 of study
  • Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min within 30 days of day 1 of study
  • Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 30 days of day 1 of study
  • 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, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to enrollment and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Human immunodeficiency virus (HIV)-patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, however HIV-positive patients must meet the following criteria: * A stable regimen of highly active anti-retroviral therapy (HAART) * No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections * A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test

Exclusion Criteria

  • Prior systemic therapy with a MEK inhibitor
  • History of another malignancy * Exception: patients who have been disease-free for 3 years or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) medical monitor if unsure whether second malignancies meet the requirements specified above
  • History of interstitial lung disease or pneumonitis requiring supplemental oxygen or treatment with oral or intravenously administered corticosteroids
  • Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity (e.g. doxorubicin), biologic therapy, or immunotherapy within 21 days prior to enrollment and/or daily or weekly chemotherapy (e.g. sunitinib, sorafenib and pazopanib) without the potential for delayed toxicity within 14 days prior to enrollment
  • Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib and during the study
  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO)
  • Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: * Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed) * Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis * The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John’s wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
  • History or current evidence/risk of retinal vein occlusion (RVO)
  • History or evidence of cardiovascular risk including any of the following: * LVEF < LLN (lower limit of normal range) * A QT interval corrected for heart rate using the Bazett’s formula QTcB >= 480 msec * History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible) * History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization * History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system * Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy * Patients with intra-cardiac defibrillators * Known cardiac metastases
  • Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible)
  • Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures
  • The study drug must not be administered to pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable)
  • Inability to comply with protocol-required procedures

Locations & Contacts

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: Temporarily closed to accrual
Name Not Available
Phone: 650-498-7061 Email: ccto-office@stanford.edu

Colorado

Aurora
University of Colorado Hospital
Status: Active
Contact: Victor Manuel Villalobos
Phone: 720-848-0650

Connecticut

New Haven
Smilow Cancer Center / Yale-New Haven Hospital
Status: Active
Contact: Hari A. Deshpande
Phone: 203-785-5702 Email: canceranswers@yale.edu
Yale University
Status: Active
Contact: Hari A. Deshpande
Phone: 203-785-5702 Email: canceranswers@yale.edu

Illinois

Chicago
Northwestern University
Status: Active
Contact: Mark Agulnik
Phone: 312-695-1301 Email: cancer@northwestern.edu

Kansas

Fairway
University of Kansas Clinical Research Center
Status: Active
Contact: Benjamin C. Powers
Phone: 913-945-7552 Email: ctnursenav@kumc.edu

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Christian Frederick Meyer
Phone: 410-955-8804 Email: jhcccro@jhmi.edu

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Active
Contact: Edwin Choy
Phone: 617-667-9925
Brigham and Women's Hospital
Status: Active
Contact: Edwin Choy
Phone: 888-823-5923 Email: ctsucontact@westat.com
Dana-Farber Cancer Institute
Status: Active
Contact: Edwin Choy
Phone: 877-442-3324
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Edwin Choy
Phone: 877-726-5130

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Contact: Scott Michael Schuetze
Phone: 800-865-1125
University of Michigan Comprehensive Cancer Center EDDOP
Status: Active
Contact: Scott Michael Schuetze
Phone: 800-865-1125

Missouri

Creve Coeur
Siteman Cancer Center at West County Hospital
Status: Active
Contact: Brian Andrew Van Tine
Phone: 800-600-3606 Email: info@siteman.wustl.edu
Saint Louis
Washington University School of Medicine
Status: Active
Contact: Brian Andrew Van Tine
Phone: 800-600-3606 Email: info@siteman.wustl.edu

Nebraska

Omaha
University of Nebraska Medical Center
Status: Active
Contact: Nicole Annette Shonka
Phone: 402-559-6941 Email: unmcrsa@unmc.edu

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Joseph Anthony Sparano
Phone: 718-904-2730 Email: aecc@aecom.yu.edu
Montefiore Medical Center-Einstein Campus
Status: Active
Contact: Joseph Anthony Sparano
Phone: 718-904-2730 Email: aecc@aecom.yu.edu
Montefiore Medical Center-Weiler Hospital
Status: Temporarily closed to accrual
Contact: Joseph Anthony Sparano
Phone: 718-904-2730 Email: aecc@aecom.yu.edu
New York
Columbia University / Herbert Irving Cancer Center
Status: Active
Contact: Gary K. Schwartz
Phone: 212-305-8615

North Carolina

Durham
Duke University Medical Center
Status: Active
Contact: James L. Abbruzzese
Phone: 888-275-3853

Ohio

Cleveland
Cleveland Clinic Foundation
Status: Active
Contact: Dale R. Shepard
Phone: 866-223-8100 Email: CancerAnswer@ccf.org
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Contact: Gabriel Ricardo Tinoco Suarez
Phone: 800-293-5066 Email: Jamesline@osumc.edu

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: Active
Contact: Margaret von Mehren
Phone: 215-728-4790
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Melissa Amber (Moidel) Burgess
Phone: 412-647-8073

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Elizabeth Jane Davis
Phone: 800-811-8480

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available
Phone: 877-312-3961

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Contact: Jonathan Whisenant
Phone: 801-581-4477 Email: clinical.trials@hci.utah.edu

Trial Objectives and Outline

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.

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

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Michigan Comprehensive Cancer Center EDDOP

Principal Investigator
Scott Michael Schuetze

Trial IDs

Primary ID 10015
Secondary IDs NCI-2017-00712, SARC033
Clinicaltrials.gov ID NCT03148275