Cancer MedDRA version: 18.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: PT Classification code 10061268 Term: Malignant nervous system neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Sanofi-aventis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1 Part (dose escalation): Patients with a 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. All patients must have measurable disease. Patients with diffuse pontine glioma are eligible without a biopsy after evidence of progressive disease post radiation therapy. Phase 2 Part (safety and activity): Patients with recurrent or refractory high grade glioma or diffuse intrinsic pontine glioma for whom no further effective therapy is available. All patients must have measurable disease. Patients with diffuse pontine glioma are eligible without a biopsy after evidence of progressive disease post radiation therapy. Patients with a grade III or grade IV glioma must have pathologic conformation either at the time of initial diagnosis or at the time of recurrence. Patients aged =2 years and =18 years Patients should meet the body surface area (BSA) requirements to be eligible: a) Minimal BSA requirements for a particular dose level; b) During the Phase 1 part patients must have a BSA 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 performance score Patients must have adequate liver, renal and marrow function as defined below: a) Total bilirubin =1.0 x the upper limit of normal (ULN) for age b) AST (SGOT) and ALT (SGPT) =2.5 x ULN c) Serum creatinine =1.5 x ULN for age or creatinine clearance =60 mL/min/1.73 m² d) Absolute neutrophil count =1.0x10^9 /L e) Platelets =75x10^9/L (transfusion independent) f) 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 the patient and/or 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 1before entering the study Are the trial subjects under 18? yes Number of subjects for this age range: 57 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Prior treatment within the following timeframes: a) Systemic anti-cancer treatment within 3 weeks (6 weeks for nitrosourea, mitomycin and monoclonal antibodies including bevacizumab) b) Surgery or smaller field radiation therapy within 4 weeks c) 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 radioimmunoconjugates lacking myelosuppressive properties) 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 requirements. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency-syndrome (AIDS)-related disease Known history of hepatitis C or known active hepatitis B infection. 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 or GCSF. 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 procédures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1 - Maximally tolerated dose of cabazitaxel 2 - Antitumor activity by evaluating the objective response rate (ORR) for patients with recurrent or refractory high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG);Timepoint(s) of evaluation of this end point: Up to 18 months;Main Objective: Phase 1 Part: To determine the dose limiting toxicity (DLT) and 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. Phase 2 Part: To determine the objective response rate (complete and partial response) and the duration of response to cabazitaxel as a single agent in patients with recurrent or refractory high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG).;Secondary Objective: Phase 1 Part: To characterize the safety and tolerability of cabazitaxel in patients with recurrent or refractory solid tumors including tumors of the central nervous system. To characterize the pharmacokinetic (PK) profile of cabazitaxel in patients with recurrent or refractory solid tumors including tumors of the central nervous system. To evaluate preliminary anti-tumor activity that may be associated with cabazitaxel in patients with recurrent or refractory solid tumors including tumors of the central nervous system. Phase 2 Part: To characterize the safety and tolerability of cabazitaxel in patients with recurrent or refractory HGG or DIPG. To estimate progression free survival in patients with recurrent or refractory HGG or DIPG. To estimate overall survival in patients with recurrent or refractory HGG or DIPG. To characterize the plasma PK profile of cabazitaxel in patients with recurrent or refractory HGG or DIPG. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Number of adverse events for patients with recurrent or refractory solid tumors including tumors of the central nervous system 2 - Pharmacokinetics: AUC 3 - Pharmacokinetics: CL 4 - Pharmacokinetics: Vss 5 - Pharmacokinetics: Cmax 6 - Preliminary anti-tumor activity in patients with recurrent or refractory solid tumors including tumors of the central nervous system 7 - Progression free survival in patients with recurrent or refractory HGG or DIPG 8 - Overall survival in patients with recurrent or refractory HGG or DIPG;Timepoint(s) of evaluation of this end point: Up to 36 months | — |
Countries
Canada, United States
Contacts
Public ContactTrial Transparency Team
Sanofi-aventis Research and Development
Outcome results
None listed