A Phase III, Double Blind, Randomized, Placebo-Controlled Trial of Sorafenib in Desmoid Tumors or Aggressive Fibromatosis (DT/DF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 298
- 主要终点
- Progression-free Survival(PFS) Rate
研究概览
简要总结
This randomized phase III trial compares the effects, good and/or bad, of sorafenib tosylate in treating patients with desmoid tumors or aggressive fibromatosis. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. [Funding Source - FDA OOPD]
详细描述
PRIMARY OBJECTIVES:
I. To compare the progression-free survival (PFS) rates of patients with desmoid tumors (DT)/deep fibromatosis (DF) who receive either sorafenib (sorafenib tosylate) or placebo using a double-blinded randomized phase III study.
SECONDARY OBJECTIVES:
I. To assess toxicity. II. To assess time to surgical intervention. III. To assess tumor response rates and survival.
TERTIARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have confirmation of DT/DF by local pathologist prior to registration
- •Patients may have been treated with locoregional therapies such as major surgery, radiation, radiofrequency ablation, or cryosurgery provided this has been completed at least 4 weeks prior to registration and recovered from therapy related toxicity to less than CTCAE grade 2
- •Patients may have been treated with cytotoxic, biologic (antibody), immune or experimental therapy, tyrosine kinase inhibitors, hormone inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs) provided this has been completed at least 4 weeks prior to registration (6 weeks for mitomycin and nitrosoureas) and recovered from any therapy related toxicity to less than CTCAE grade 2
- •Patients with prior or current treatment of sorafenib are excluded
- •No concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted; please note that drugs that strongly induce or inhibit cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or are associated with a risk of torsades are not allowed; chronic concomitant treatment of CYP3A4 inducers is not allowed (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's wort); as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; the following drugs are strong inhibitors of CYP3A4 and are not allowed during the treatment with sorafenib:
- •Boceprevir
- •Indinavir
- •Nelfinavir
- •Lopinavir/ritonavir
- •Saquinavir
- •Telaprevir
- •Ritonavir
- •Clarithromycin
- •Conivaptan
- •Itraconazole
- •Ketoconazole
- •Mibefradil
- •Nefazodone
- •Posaconazole
- •Voriconazole
- •Telithromycin
- •Drugs with possible or conditional risk of torsades should be used with caution knowing that sorafenib could prolong the QT interval
- •Chronic daily NSAID use as treatment for controlling desmoid tumors is not allowed, and should be stopped >= 3 days prior to registration; NSAIDS are allowed when used for desmoid tumor-related pain or for symptoms that are unrelated to desmoid disease (eg. headache, arthritis)
- •Patients must have measurable disease
- •Patients have to meet one of the following criteria to be eligible:
- •Disease determined unresectable or entailing unacceptably morbid surgery based on 1 or more of the following characteristics:
- •Multifocal disease
- •Disease in which there is involvement or inadequate plane from: neurovascular bundle, bone, skin, or viscera
- •Large size in relationship to location OR multi-compartment involvement
- •Progression by radiographic imaging (10% increase in size by RECIST v1.1 within 6 months of registration)
- •Patients with symptomatic disease which meets the following criteria Brief Pain Inventory (BPI) score greater than or equal to 3 AND one of the following:
- •Inability to control pain with NSAIDs and considering addition of narcotics OR
- •> 30% increase in current use of narcotics OR
- •Addition of a new opioid narcotic
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Patients who are pregnant or nursing are not eligible
- •No patients with a history of cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); active coronary artery disease (CAD) (myocardial infarction or unstable angina within 6 months prior to study entry)
- •No patients with inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 90 mmHg diastolic), or any prior history of hypertensive crisis or hypertensive encephalopathy
- •No patients with clinically significant gastrointestinal (GI) bleeding or bleeding diathesis within 30 days prior to registration
- •Absolute neutrophil count >= 1,500/mm^3
- •Hemoglobin >= 8 g/dl
- •Platelets >= 75,000/mm^3
- •Total bilirubin =< 1.5 x upper limits of normal (ULN)
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamate pyruvate transaminase (SGPT) (aspartate aminotransferase [ALT]) =< 1.5 x ULN
- •Calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault equation
排除标准
- 未提供
研究组 & 干预措施
Arm I (sorafenib tosylate)
Patients receive sorafenib tosylate PO QD on days 1-28.
干预措施: Sorafenib Tosylate (Drug)
Arm II (placebo)
Patients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression.
干预措施: Quality-of-Life Assessment (Other)
Arm I (sorafenib tosylate)
Patients receive sorafenib tosylate PO QD on days 1-28.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo)
Patients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (sorafenib tosylate)
Patients receive sorafenib tosylate PO QD on days 1-28.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo)
Patients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression.
干预措施: Placebo Administration (Other)
结局指标
主要结局
Progression-free Survival(PFS) Rate
时间窗: Time from randomization to the first occurrence of progression or death due to any cause, assessed up to 3 years
PFS is defined as the time from randomization to the first occurrence of progression or death due to any cause. If no event exists, the PFS will be censored at the last disease assessment. Data following cross over will be analyzed and summarized separately from the data from the main course of treatment for these patients in an exploratory and hypothesis generating manner. Intention to treat principles will be used. Patient disease status was evaluated using RECSIT v1.1. Patients ending treatment for symptomatic deterioration without radiographic evidence of PD, were classified as having PD. Otherwise, patients not yet showing disease progression were classified as having no progression at the most recent disease assessment and in the following cases: crossing over to receive sorafenib, date of first non-protocol directed anti-cancer therapy, lost to follow-up, withdrawal of consent, and changing imaging methods from that which was used at study entry.
次要结局
- Best Objective Status Between the Two Treatment Arms According to Response Evaluation Criteria in Solid Tumors Version 1.1(Up to 3 years)
- Incidence of Adverse Events, Using the Patient Reported Outcomes-Common Terminology Criteria in Adverse Events Version 4.0(Up to 3 years)
- Overall Survival(Time between the date of randomization to until death, assessed up to 3 years)
- Time to Surgical Intervention During Treatment(Time between randomization to the patient undergoing therapeutic surgical resection for this disease, assessed up to 3 years)
- Duration of Response(Time between first tumor response and progression, assessed up to 3 years)