A Phase II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib in Children and Young Adults With Relapsed/Refractory Rhabdomyosarcoma, Wilms Tumor, Hepatocellular Carcinoma, and Papillary Thyroid Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 92
- 主要终点
- Objective Response by RECIST Criteria v 1.1
研究概览
简要总结
This phase II trial studies how well sorafenib tosylate works in treating younger patients with relapsed or refractory rhabdomyosarcoma, Wilms tumor, liver cancer, or thyroid cancer. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the objective response rate to sorafenib tosylate (sorafenib) in children with relapsed or refractory rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), or papillary thyroid carcinoma (PTC).
SECONDARY OBJECTIVES:
I. To further define and describe the toxicities of sorafenib administered on an oral, twice-daily continuous schedule.
II. To further characterize the pharmacokinetics of sorafenib in children with refractory cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:
- •Rhabdomyosarcoma (RMS)
- •Wilms tumor
- •Hepatocellular carcinoma (HCC)
- •Papillary thyroid carcinoma (PTC)
- •Patients must have relapsed or refractory disease (RMS, Wilms tumor, HCC, PTC)
- •Patients must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
- •The following do not qualify as measurable disease:
- •Malignant fluid collections (e.g., ascites, pleural effusions)
- •Bone marrow infiltration
- •Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or positron emission tomography [PET] scans)
- •Elevated tumor markers in plasma or cerebrospinal fluid(CSF)
- •Previously radiated lesions that have not demonstrated clear progression post radiation
- •Leptomeningeal lesions that do not meet the requirements noted above
- •Patients with HCC must be relapsed or refractory to conventional chemotherapy
- •Patients with PTC must be refractory to radioactive iodine (RAI)
- •Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- •Patients with known metastasis to the brain will be excluded from trial participation unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months
- •Rhabdomyosarcoma and Wilms strata: patients must be ≥ 24 months and ≤ 30 years of age at study enrollment
- •Hepatocellular carcinoma (HCC): patients must be ≥ 24 months and < 18 years of age at study enrollment
- •Papillary thyroid carcinoma (PTC): patients must be ≥ 24 months and ≤ 21 years of age at study enrollment
- •Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories 0, 1, or 2
- •Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age
- •Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- •Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
- •Platelet count ≥ 75,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
- •Hemoglobin 8.0 g/dL (may receive red blood cell[RBC] transfusions)
- •Creatinine clearance or radioisotope glomerular filtration rate(GFR) 70 mL/min OR a serum creatinine based on age/gender as follows:
- •0.8 mg/dL (2 to < 6 years of age)
- •1.0 mg/dL (6 to < 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- •1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- •SGPT (ALT) ≤ 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
- •PT, PTT, and INR < 1.5 times ULN
- •Normal serum lipase and amylase (per institutional normal values)
- •No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination
- •A blood pressure (BP) ≤ the 95^th percentile for age, height, and gender; and not receiving medication for treatment of hypertension
- •Patients who are pregnant or breast-feeding are not eligible
- •Negative pregnancy tests must be obtained in girls who are post-menarchal
- •Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of the informed consent until at least 30 days after the last dose of the study drug
- •Patients with clinical symptoms of hepatic encephalopathy or ascites are not eligible
- •Patients who have an uncontrolled infection are not eligible
- •Patients with evidence of bleeding diathesis are not eligible
- •Patients with known Gilbert syndrome are not eligible
- •Patients who, in the opinion of the investigator, may not be able to comply with the safety-monitoring requirements of the study are not eligible
- •No concurrent chemotherapy, radiation therapy, immunomodulating agents, or other investigational agents
- •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- •Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
- 另有 15 项未显示
排除标准
- 未提供
研究组 & 干预措施
Group 1 Relapsed/Refractory Rhabdomyosarcoma
Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: sorafenib tosylate (Drug)
Group 1 Relapsed/Refractory Rhabdomyosarcoma
Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: pharmacological study (Other)
Group 1 Relapsed/Refractory Rhabdomyosarcoma
Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: laboratory biomarker analysis (Other)
Group 2 Relapsed/Refractory Wilms tumor
Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: sorafenib tosylate (Drug)
Group 2 Relapsed/Refractory Wilms tumor
Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: pharmacological study (Other)
Group 2 Relapsed/Refractory Wilms tumor
Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: laboratory biomarker analysis (Other)
Group 3 Relapsed/Refractory hepatocellular carcinoma
Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: sorafenib tosylate (Drug)
Group 3 Relapsed/Refractory hepatocellular carcinoma
Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: pharmacological study (Other)
Group 3 Relapsed/Refractory hepatocellular carcinoma
Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: laboratory biomarker analysis (Other)
Group 4 Papillary thyroid carcinoma
Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: sorafenib tosylate (Drug)
Group 4 Papillary thyroid carcinoma
Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: pharmacological study (Other)
Group 4 Papillary thyroid carcinoma
Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
sorafenib tosylate: Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28
pharmacological study: Optional correlative studies
laboratory biomarker analysis: Optional correlative studies
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Objective Response by RECIST Criteria v 1.1
时间窗: 6 cycles (168 days)
Response rates will be calculated as the number of evaluable patients who are responders. Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Progression-free Survival According to RECIST Version 1.1(Six months after enrollment)
- The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity,(six cycles of chemotherapy; expected to be 126 days of treatment)
- Pharmacokinetic (PK) Parameters of Sorafenib Tosylate(Prior to administration of Sorafenib (baseline), day 15, day 56, day 112 and day 168)
- Change in VEGF and VEGFR-2(Prior to the administration of sorafenib (baseline) and day 15 of protocol therapy)
- Presence of BRAF Mutation or RET/PTC Rearrangement(At baseline)