AzTrials
AzTrials

Locally Advanced Epithelioid HemangioendotheliomaPhase 2NCT03148275

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

A Phase 2 study testing Questionnaire Administration and Trametinib in people with Locally Advanced Epithelioid Hemangioendothelioma and Metastatic Epithelioid Hemangioendothelioma, run by National Cancer Institute (NCI) at 36 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 (metastatic), nearby tissue or lymph nodes (locally advanced), or cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Questionnaire Administration and Trametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
36 sitesUnited States
Study dates
20 Jun 2017to 23 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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), and tumor tissue (paraffin-embedded tissue block or tumor tissue on unstained glass slides) available for fusion fluorescence in situ hybridization (FISH) analysis at Cleveland Clinic; patient tumor tissue stored in pathology archives may be used for fusion FISH; a new biopsy is not mandatory
  • 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
  • Because there is no established standard or approved drug therapy for treatment of epithelioid hemangioendothelioma (EHE), patients previously untreated or treated with drug therapy for 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
Show all 21Show fewer
  • 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 2 weeks of patient registration)
  • Hemoglobin >= 9 g/dL, patients may receive transfusion to meet criterion (within 2 weeks of patient registration)
  • Platelets >= 75 x 10^9/L (within 2 weeks of patient registration)
  • Albumin >= 2.5 g/dL (within 2 weeks of patient registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks of patient registration); 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 2 weeks of patient registration)
  • 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 2 weeks of patient registration)
  • Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) (within 30 days of registration)
  • Trametinib can cause fetal harm when administered to a pregnant woman; 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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
  • Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, 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:
  • 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
  • Trametinib was embryotoxic and abortifacient in rabbits at doses greater than or equal to those resulting in exposures approximately 0.3 times the human exposure at the recommended clinical dose. Therefore, 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

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

United States36 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Questionnaire Administration, Trametinib
Medical subject headings
Hemangioendothelioma, Epithelioid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Questionnaire AdministrationOther

    Ancillary studies

  • TrametinibDrug

    Also called GSK 1120212, GSK-1120212, GSK1120212, JTP-74057

    Given PO

Study groups in NCT03148275
Study groupRoleWhat they receive
Treatment (trametinib)ExperimentalPatients 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.
Receives: Other: Questionnaire Administration; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    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.

    Measured: 6 months

Secondary outcomes (5)

  1. 6 Month Progression-free Survival

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

    Measured: 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

  2. Overall Survival

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

    Measured: From the time of first dose of study drug to occurrence of death from any cause, assessed at 2 years

  3. Incidence of Adverse Events

    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.

    Measured: at 6 months

  4. Change in Patient Reported Symptoms

    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. PROMIS questionnaires were scored according to recommended standardized system and T-scores. A Wilcoxon signed rank test was used to assess the change in scores/T-scores over time. Determination of change in score between timepoints only included patients that had scores at those timepoints.

    Pain Intensity - 3a Scale: 36.3 (no pain) - 81.8 (severe pain) Pain Interference - 4a Scale: 41.6 (no interference) - 75.6 (large interference) Pain Behavior - 7a Scale: 34.1 (had no pain) - 78.9 (always in pain) Global Mental Heath Scale: 21.2 (severe) - 67.6 (none) Global Mental Physical Scale: 16.2 (severe) - 67.7 (none)

    Measured: Baseline and at 6 months

  5. Median Progression-free Survival

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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2017
  2. Study start20 Jun 2017
  3. Primary completion23 Jun 2023
  4. Study completion23 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03148275
Sponsor's protocol ID
NCI-2017-00712
Other IDs
NCI-2017-00712, SARC033, 10015, 10015, P30CA046592
Status last verified
Nov 2024
First submitted
1 May 2017
Last updated
26 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ma S, Kanai R, Pobbati AV, Li S, Che K, Seavey CN, Hallett A, Burtscher A, Lamar JM, Rubin BP. The TAZ-CAMTA1 Fusion Protein Promotes Tumorigenesis via Connective Tissue Growth Factor and Ras-MAPK Signaling in Epithelioid Hemangioendothelioma. Clin Cancer Res. 2022 Jul 15;28(14):3116-3126. doi: 10.1158/1078-0432.CCR-22-0421.

    PubMed 35443056

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Questionnaire Administration and Trametinib in people with Locally Advanced Epithelioid Hemangioendothelioma and Metastatic Epithelioid Hemangioendothelioma, run by National Cancer Institute (NCI) at 36 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03148275, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in