A Phase I Dose Escalation Study of Cabazitaxel in Pediatric Patients with Refractory Solid Tumors including Tumors of the Central Nervous System
To determine the maximum tolerated dose (MTD) of cabazitaxel as a single agent in pediatric patients with recurrent or refractory solid tumors including tumors of the central nervous system.
Ages Eligible for Study: 2 Years to 18 Years Genders Eligible for Study: Both Accepts Healthy Volunteers: No Criteria Inclusion criteria : â?¢Patients with histologically confirmed solid tumor including tumors of the central nervous system that is recurrent or refractory and for which no further effective standard treatment is available. Patients with diffuse pontine glioma are eligible without a biopsy after evidence of progressive disease post radiation therapy. 1.Dose escalation: Patients aged â?¥5 years and â?¤18 years 2.Safety expansion: Patients aged â?¥2 years and â?¤18 years â?¢Patients should meet the minimal body surface area (BSA) requirements to be eligible for a particular dose level; for safety reasons during dose escalation patients must have a starting BSA less than 2.1m2 â?¢Performance status by: 1.Lansky score â?¥60 (patients â?¤10 years of age) 2.Karnofsky score â?¥60% (patients greater than 10 years of age) â?¢Patients who are unable to walk because of paralysis, but who are mobile in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score â?¢Patients must have adequate liver, renal and marrow function as defined below: 1.Total bilirubin â?¤1.0 x the upper limit of normal (ULN) for age 2.AST (SGOT) and ALT (SGPT) â?¤2.5 x ULN, 3.Serum creatinine â?¤1.5 x ULN for age or creatinine clearance â?¥60 mL/min/1.73 m2 4.Absolute neutrophil count â?¥1.0x109/L 5.Platelets â?¥75x109/L (transfusion independent) 6.Hemoglobin â?¥ 8.0 g/dL (can be transfused) â?¢Female patients of child-bearing potential must have a negative pregnancy test â?¤ 7 days before starting cabazitaxel treatment. â?¢Male and female patients of reproductive potential must agree to use adequate contraception prior to study entry, for the duration of study participation and for 6 months following the last dose of cabazitaxel. â?¢Written informed consent/assent prior to any study-specific procedures. Consent must be obtained from parent(s) or legal guardian(s) and the signature of at least one parent or guardian will be required. Investigators will also obtain assent of patients according to local, regional or national guidelines. â?¢Patients must have recovered from the acute toxic effects of all prior therapy to â?¤ grade 1 before entering this study Exclusion criteria: â?¢Prior treatment within the following timeframes: 1.Systemic anti-cancer treatment within 3 weeks (6 weeks for nitrosourea, mitomycin and monoclonal antibodies) 2.Surgery or smaller field radiation therapy within 4 weeks 3.Treatment with an investigational agent within 4 weeks or within 5 half-lives of the agent, whichever is longer â?¢Craniospinal or other large field radiation therapy (defined as greater than 25% of bone marrow irradiated) within 6 months prior to the first dose. â?¢Prior systemic radioisotope therapy (this does not include diagnostic imaging) or total body irradiation â?¢Prior bone marrow or stem cell transplant â?¢Patients with any clinically significant illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy, would compromise a patient's ability to tolerate cabazitaxel or result in inability to assess toxicity. This includes, but is not limited to uncontrolled intercurrent illness including ongoing or active infection, cardiac disease, renal impairment, planned surgery or psychiatric illness/social situations that would limit compliance with study requirements. â?¢Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency-syndrome (AIDS)-related disease â?¢Active hepatitis â?¢Pregnant or breast feeding women â?¢Treatment with strong inhibitors or strong inducers of CYP3A4 or enzyme inducing anti-epileptic drugs (EIAED) within 14 days prior to first dose of cabazitaxel and for the duration of study. Non-EIAEDs are permitted. â?¢Known history of hypersensitivity to taxanes or polysorbate 80. â?¢Participation in another interventional clinical trial and/or concurrent treatment with any investigational drug. â?¢Patients not able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Experimental: Dose escalation and expansion Cabazitaxel will be administered intravenously on Day 1 of each 21-day cycle. Cycle administration will be repeated every 3 weeks. From an initial starting dose (dose level 1) the dose of cabazitaxel will be escalated during subsequent cycles. Premedications will also be administered prior to each dose of cabazitaxel (antihistamine + steroid + H2 antagonist). Patients will start G-CSF or Peg G-CSF at least 24 hours after completion of the cabazitaxel infusion
04/18/2014 04:02 AM