A Phase I Dose Escalation Study of Cabazitaxel in Pediatric Patients With Refractory Solid Tumors Including Tumors of the Central Nervous System
Inclusion criteria :
- 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 ≥5 years and ≤18 years
2. Safety expansion: Patients aged ≥2 years and ≤18 years
- 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 < 2.1m2
- Performance status by:
1. Lansky score ≥60 (patients ≤10 years of age)
2. Karnofsky score ≥60% (patients >10 years of age)
- 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
- Patients must have adequate liver, renal and marrow function as defined below:
1. Total bilirubin ≤1.0 x the upper limit of normal (ULN) for age
2. AST (SGOT) and ALT (SGPT) ≤2.5 x ULN,
3. Serum creatinine ≤1.5 x ULN for age or creatinine clearance ≥60 mL/min/1.73 m2
4. Absolute neutrophil count ≥1.0x109/L
5. Platelets ≥75x109/L (transfusion independent)
6. Hemoglobin ≥ 8.0 g/dL (can be transfused)
- Female patients of child-bearing potential must have a negative pregnancy test ≤ 7
days before starting cabazitaxel treatment.
- 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.
- 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.
- Patients must have recovered from the acute toxic effects of all prior therapy to ≤
grade 1 before entering this study
- 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
- Craniospinal or other large field radiation therapy (defined as >25% of bone marrow
irradiated) within 6 months prior to the first dose.
- Prior systemic radioisotope therapy (this does not include diagnostic imaging) or
total body irradiation
- Prior bone marrow or stem cell transplant
- 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
- Known human immunodeficiency virus (HIV) infection or acquired
immunodeficiency-syndrome (AIDS)-related disease
- Active hepatitis
- Pregnant or breast feeding women
- 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.
- Known history of hypersensitivity to taxanes or polysorbate 80.
- Participation in another interventional clinical trial and/or concurrent treatment
with any investigational drug.
- Patients not able to comply with scheduled visits, treatment plans, laboratory tests,
and other study procedures.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.