PNOC031: Protocol for Embryonal Tumor With Multilayered Rosettes (ETMR)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 8
- 主要终点
- Median Progression-free survival at 6 months (PFS6) (Cohort 1)
研究概览
简要总结
This is an open-label, comprehensive, iterative investigation of evaluating the use of induction chemotherapy, high-dose chemotherapy, and focal radiation therapy in children with newly diagnosed Embryonal Tumor With Multilayered Rosettes (ETMR).
详细描述
PRIMARY OBJECTIVES I. To determine the six-month progression-free survival (PFS6) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR, treated using a regimen of induction chemotherapy and early focal radiotherapy (Cohort 1)
SECONDARY OBJECTIVES I. To determine the two-year progression-free survival (PFS) and overall survival (OS) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR (Cohort 1).
II. To determine the two-year progression-free survival (PFS) and overall survival (OS) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR (Cohort 2).
III. To determine the two-year progression-free survival (PFS), overall survival (OS) and objective response rate of participants with newly diagnosed, incompletely resected and/or metastatic ETMR (Cohort 3A and 3B)
EXPLORATORY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The eligibility criteria listed below are interpreted literally and cannot be waived.
- •Inclusion Criteria:
- •Participants must have either a molecularly or histologically confirmed embryonal tumor with multilayered rosettes.
- •For enrollment, a confirmation of a minimum of 10-20 unstained formalin-fixed paraffin-embedded (FFPE) slides or 1 block (15-20 mg) with tumor content of 40% or greater is required. Anything less must be discussed and approved by the study chairs prior to enrollment.
- •Prior Therapy:
- •Cohort 1 participants must not have received any prior tumor-directed therapy other than surgical resection.
- •Cohort 2 and 3 participants may receive tumor-directed therapy prior to enrollment. These participants must be discussed with study chairs prior to enrollment.
- •Participants must not have received prior radiation for treatment of tumor.
- •Participants of any age are eligible.
- •Participants should begin induction chemotherapy within 28 days of the most recent definitive surgical procedure. Participants beginning therapy beyond 28 days from surgery, will need to discuss with study chairs.
- •Cohort specific eligibility
- •Cohort 1: Gross-total resection, Eligible for early radiotherapy (please see age criteria below), and no evidence of metastatic disease.
- •Cohort 2: Gross-total resection, high dose chemotherapy (please see age criteria below), and no evidence of metastatic disease.
- •Cohort 3A: Metastatic or residual disease, and early radiotherapy.
- •Cohort 3B: Metastatic or residual disease, and high dose chemotherapy.
- •Radiotherapy Age Criteria (at the time of planned radiation): >12 months of age for participants with infratentorial tumor OR >15 months of age for participants with supratentorial tumor. For participants being treated on radiotherapy-containing arms, the legal parent/guardian or patient and the physician must be willing to allow the use of radiotherapy for treatment.
- •Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <=16 years of age. Participants 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.
- •Organ Function Requirements:
- •Peripheral absolute neutrophil count (ANC) > 75,000/mm3
- •Platelet count > 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 72 hours prior to enrollment).
- •Adequate Renal Function defined as:
- •a. Serum creatinine < 1.5 x upper limit normal (ULN) based on age and gender.
- •Adequate Liver Function defined as:
- •Total bilirubin < 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN,
- •alanine aminotransferase (ALT) < 3 x ULN,
- •aspartate aminotransferase (AST) < 3 x ULN,
- •Adequate Neurologic Function defined as:
- •a. Participants with seizure disorder may be enrolled if well controlled. Participants on enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drugs.
- •As chemotherapeutic agents used in this trial are known to be teratogenic, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of study therapy. 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.
- •Participants must be enrolled on PNOC COMP prior to enrollment on PNOC031 if PNOC COMP is open to accrual at the enrolling institution.
- •A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
排除标准
- •Cohort 1 only: Participants who have received any prior tumor-directed therapy other than surgical intervention
- •Participants who are receiving any other tumor directed investigational agents.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study.
- •Uncontrolled intercurrent illness.
- •Women of childbearing potential must not be pregnant or breast-feeding.
研究组 & 干预措施
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Radiotherapy (RT) (Radiation)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Non-Investigational Surgical Resection (Procedure)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Tumor Tissue Sample (Procedure)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Blood Sample (Procedure)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Cerebrospinal Fluid (CSF) Sample (Procedure)
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Temozolomide (Drug)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Temozolomide (Drug)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Temozolomide (Drug)
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Non-Investigational Surgical Resection (Procedure)
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Tumor Tissue Sample (Procedure)
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Cerebrospinal Fluid (CSF) Sample (Procedure)
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Blood Sample (Procedure)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Non-Investigational Surgical Resection (Procedure)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Chemotherapy Drug, Cancer - Physician's Choice (Drug)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Temozolomide (Drug)
Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
干预措施: Chemotherapy Drug, Cancer - Physician's Choice (Drug)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Radiotherapy (RT) (Radiation)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Chemotherapy Drug, Cancer - Physician's Choice (Drug)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Non-Investigational Surgical Resection (Procedure)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Tumor Tissue Sample (Procedure)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Blood Sample (Procedure)
Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
干预措施: Cerebrospinal Fluid (CSF) Sample (Procedure)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Radiotherapy (RT) (Radiation)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Chemotherapy Drug, Cancer - Physician's Choice (Drug)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Tumor Tissue Sample (Procedure)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Blood Sample (Procedure)
Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
干预措施: Cerebrospinal Fluid (CSF) Sample (Procedure)
Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
干预措施: Radiotherapy (RT) (Radiation)
结局指标
主要结局
Median Progression-free survival at 6 months (PFS6) (Cohort 1)
时间窗: Up to 6 months
The median PFS6 is defined as the median number of months for participants in Cohort 1 who have remained progression-free from the date of initial surgical resection until 6 months.
次要结局
- Median Progression-free survival at 2 years progression-free survival (PFS)(Up to 2 years)
- Median Overall Survival at 2 years (OS)(Up to 2 years)