A Phase 1/2, Multicenter, Open-label, Dose-finding Study to Assess the Safety, Tolerability, and Preliminary Efficacy of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent or Refractory Solid Tumors.

Celgene20 个研究点分布在 7 个国家目标入组 107 人开始时间: 2013年12月4日最近更新: 2019年12月27日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Celgene
入组人数: 107
试验地点: 20
主要终点: Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.

详细描述

ABI-007-PST-001 is a Phase 1/2, multicenter, open-label, dose-finding study to assess the safety , tolerability, and preliminary efficacy of weekly nab-paclitaxel in pediatric patients with recurrent or refractory solid tumors (excluding brain tumors). The Phase 1 portion of the study, with a dose escalation design, ended and the recommended Phase 2 dose (RP2D) was determined as 240 mg/m^2 intravenously (IV) in patients weighing > 10 kg and 11.5 mg/kg in patients weighing ≤ 10 kg, on Days 1, 8 and 15 of a 28-day cycle. The Phase 2 portion of the study will enroll additional patients at the RP2D into 1 of 3 solid tumor groups [neuroblastomas, rhabdomyosarcomas, Ewing's sarcomas]. Both phases of the study are open-label and conducted at multiple centers.

The Phase 2 is using a Simon 2-stage design to monitor patient enrollment for each group separately. The rhabdomyosarcoma group, neuroblastoma or Ewing's sarcoma groups did not reach the expected number of 2 responders out of 14 efficacy eligible patients. Consequently, the groups were stopped.

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: 6 Months 至 24 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patients must meet all of the following criteria to be enrolled in the study:
•Patient has a confirmed solid tumor diagnosis according to the
•Phase 1: patient has a recurrent or refractory solid tumor that has
•progressed or did not respond to standard therapy, or for which no
•standard anticancer therapy exists
•Phase 2: patient has radiologically documented measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for neuroblastoma, evaluable disease by 123^I-metaiodobenzylguanidine [MIBG]/Curie score is also acceptable) in 1 of the following tumor types and has failed up to 3 lines of treatment: Group 1: neuroblastoma, Group 2: rhabdomyosarcoma; Group 3: Ewing's sarcoma.
•The patient has a Lansky/Karnofsky performance status score of ≥ 70%.
•The patient has adequate serum chemistry levels, evidenced by the
•following laboratory values
•aspartate aminotransferase (AST)/serum glutamic-oxaloacetric
•transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic
•pyruvate transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN)
•Total bilirubin ≤ 1.5 × ULN
•Creatinine ≤ 1.5 × ULN
•The patient has adequate bone marrow function, evidenced by the
•Absolute neutrophil count ≥ 1.0 × 10^9 cells/L
•Platelets ≥ 80 × 10^9 cells/L (transfusion independent, defined as not
•receiving platelet transfusions within 7 days prior to laboratory sample). In the phase 2 portion, for patients with known bone marrow involvement, platelets ≥ 50 × 10^9 cells/L
•Hemoglobin ≥ 8 g/dL (transfusion is permitted to fulfill this criterion).
•The patient (when applicable) or patient's parent(s) or legal guardian(s)
•understand(s) and voluntarily signed an informed consent document prior
•to any study-related assessments/procedures being conducted. Where
•locally applicable, the patient also understands and voluntarily provides
•his/her assent prior to any study-related assessments/procedures being
•Male patients of childbearing potential must use a condom during
•sexual intercourse and shall not father a child during the study and for 6 months after the last dose of study medication.
•Female patients of childbearing potential [defined as all female
•patients ≥ 12 years old or who have reached menarche, whichever occurs
•first] must have both of the following:
•a. Agree to the use of two physician-approved contraceptive methods
•simultaneously or practice complete abstinence while on study medication or for a longer period if required by regulations.
•i. True abstinence: When this is in line with the preferred and usual
•lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
•symptothermal, postovulation methods) and withdrawal are not
•acceptable methods of contraception.
•ii. Acceptable contraceptive methods include: oral, injectable, or
•implantable hormonal contraceptive; tubal ligation; intra-uterine device;
•barrier contraceptive with spermicide; or vasectomized partner) including
•at least one barrier method.
•b. Have negative serum pregnancy test result at screening confirmed by
•negative urine pregnancy dipstick within 72 hours prior to first dose of
•investigational product (if serum test occurred > 72 hours from first
•dose); pregnancy test with sensitivity of at least 25 mIU/mL.

排除标准

•The presence of any of the following will exclude a patient from enrollment:
•The patient has a primary brain tumor(s) or brain metastasis (unless metastasis is treated and stable for > 28 days). In patients who are symptomatic, a brain scan is required to exclude metastasis.
•The patient has received therapeutic dose chemotherapy or radiotherapy ≤ 21 days prior to start of investigational product.
•The patient has received maintenance dose chemotherapy (e.g., low dose cyclophosphamide) ≤ 7 days from the first dose of investigational product.
•The patient has received any investigational therapy ≤ 28 days prior to start of investigational product. Investigational therapy is defined as any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric.
•The patient has received any biological therapy ≤ 7 days prior to the start of investigational product, or monoclonal antibody ≤ 3 half-lives or 28 days, whichever is shorter, prior to the first dose of investigational product.
•The patient has received any hematopoietic stem cell transplantation (HSCT) ≤ 3 months prior to start of investigational product.
•The patient has received allogeneic hematopoietic stem cell transplantation (HSCT) ≤ 3 months or autologous HSCT ≤ 21 days prior to start of investigational product.
•The patient has not recovered from the acute toxic effects of prior chemotherapy, radiation, or major surgery/significant trauma.
•The patient has had minor surgery ≤ 7 days from the start of study treatment (excluding the placement of central/peripheral lines, skin biopsy).
•The patient has a known history of stroke, myocardial infarction, peripheral vascular disease, or recent (within 3 months) uncontrolled deep venous thrombosis.
•The patient has a known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless of treatment status.
•The patient has an uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•The patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
•The patient has any condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk if he/she were to participate in the study.
•The patient has any condition that confounds the ability to interpret data from the study.
•The patient or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator.
•The patient has ≥ Grade 2 peripheral neuropathy by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at screening.