NCT03148275已完成2 期
A Non-Randomized, Open-Label, Phase 2 Study of Trametinib in Patients With Unresectable or Metastatic Epithelioid Hemangioendothelioma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 36
- 主要终点
- Objective Response Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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
排除标准
- •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
- •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
研究组 & 干预措施
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Trametinib (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 6 months
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.
次要结局
- 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)
研究者
研究点 (36)
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