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

NCT03148275 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: NCI-2017-00712SARC03310015P30CA046592
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 36

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 (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.

Conditions

Locally Advanced Epithelioid Hemangioendothelioma; Metastatic Epithelioid Hemangioendothelioma; Unresectable Epithelioid Hemangioendothelioma

Outcome Measures

Primary Outcomes (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.

  6 months

Secondary Outcomes (5)

• 6 Month Progression-free Survival

  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

• Overall Survival

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

• Incidence of Adverse Events

  at 6 months

• Change in Patient Reported Symptoms

  Baseline and at 6 months

• Median Progression-free Survival

  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

Other Outcomes (8)

• Change in Epithelioid Hemangioendothelioma Growth Rate

  Baseline up to 6 months

• Change in CRP Level

  Baseline up to 6 months

• Change in ESR Level

  Baseline up to 6 months

Study Arms (1)

Treatment (trametinib)

EXPERIMENTAL

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.

Other: Questionnaire Administration; Drug: Trametinib

Interventions

Questionnaire Administration OTHER

Ancillary studies

Treatment (trametinib)

Trametinib DRUG

Given PO

Also known as: GSK 1120212, GSK-1120212, GSK1120212, JTP-74057, MEK Inhibitor GSK1120212

Treatment (trametinib)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (36)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Medicine-Bellevue

Bellevue, Nebraska, 68123, United States

Location

Nebraska Medicine-Village Pointe

Omaha, Nebraska, 68118, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

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

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 35443056 DERIVED

MeSH Terms

Conditions

Hemangioendothelioma, Epithelioid

Interventions

trametinib

Condition Hierarchy (Ancestors)

Hemangioendothelioma; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Scott M Schuetze

  University of Michigan Comprehensive Cancer Center EDDOP

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: May 10, 2017
• Study Start: June 20, 2017
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Locations

US (36)