Malignant Solid Tumor - Malignant Nervous System Neoplasm Clinical Trial
Official title:
A Phase 1-2 Dose Finding, Safety and Efficacy Study of Cabazitaxel in Pediatric Patients With Refractory Solid Tumors Including Tumors of the Central Nervous System
| Verified date | March 2016 |
| Source | Sanofi |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
Primary Objectives:
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 Objectives:
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.
| Status | Completed |
| Enrollment | 39 |
| Est. completion date | February 2016 |
| Est. primary completion date | July 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 2 Years to 18 Years |
| Eligibility |
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: 1. Minimal BSA requirements for a particular dose level; 2. During the Phase 1 part patients must have a BSA <2.1 m² at the time of enrollment 3. During the Phase 2 part patients with a BSA =2.1 m² will be eligible, however the actual dose of cabazitaxel for these patients will be adjusted to a maximum dose calculated with (capped at) the BSA of 2.1 m² 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 performance score 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 =1.0x10^9 /L 5. Platelets =75x10^9/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 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. Exclusion criteria: Prior treatment within the following timeframes: 1. Systemic anti-cancer treatment within 3 weeks (6 weeks for nitrosourea, mitomycin and monoclonal antibodies including bevacizumab) 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 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 G-CSF. 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. |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Canada | Investigational Site Number 124001 | Toronto | |
| United States | Investigational Site Number 840007 | Aurora | Colorado |
| United States | Investigational Site Number 840010 | Baltimore | Maryland |
| United States | Investigational Site Number 840002 | Boston | Massachusetts |
| United States | Investigational Site Number 840012 | Chicago | Illinois |
| United States | Investigational Site Number 840006 | Houston | Texas |
| United States | Investigational Site Number 840013 | Los Angeles | California |
| United States | Investigational Site Number 840003 | New York | New York |
| United States | Investigational Site Number 840005 | Orlando | Florida |
| United States | Investigational Site Number 840014 | Palo Alto | California |
| United States | Investigational Site Number 840009 | Phoenix | Arizona |
| United States | Investigational Site Number 840008 | Seattle | Washington |
| United States | Investigational Site Number 840011 | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Sanofi |
United States, Canada,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Maximally tolerated dose of cabazitaxel | Up to 18 months | No | |
| Primary | 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) | Up to 18 months | No | |
| Secondary | Number of adverse events for patients with recurrent or refractory solid tumors including tumors of the central nervous system | Up to 36 months | No | |
| Secondary | Pharmacokinetics: AUC | Up to 36 months | No | |
| Secondary | Pharmacokinetics: CL | Up to 36 months | No | |
| Secondary | Pharmacokinetics: Vss | Up to 36 months | No | |
| Secondary | Pharmacokinetics: Cmax | Up to 36 months | No | |
| Secondary | Preliminary anti-tumor activity in patients with recurrent or refractory solid tumors including tumors of the central nervous system | Up to 36 months | No | |
| Secondary | Progression free survival in patients with recurrent or refractory HGG or DIPG | Up to 36 months | No | |
| Secondary | Overall survival in patients with recurrent or refractory HGG or DIPG | Up to 36 months | No |