Safety and Efficacy of Cabazitaxel in Pediatric Patients With Refractory Solid Tumors Including Central Nervous System Tumors

This study is currently recruiting participants.
Verified March 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01751308
First received: December 13, 2012
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Malignant Solid Tumor - Malignant Nervous System Neoplasm
Drug: Cabazitaxel (XRP6258)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Maximally tolerated dose of cabazitaxel [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of adverse events for patients with recurrent or refractory solid tumors including tumors of the central nervous system [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: AUC [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: CL [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Vss [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cmax [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Preliminary anti-tumor activity in patients with recurrent or refractory tumors of the central nervous system [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Progression free survival in patients with recurrent or refractory HGG or DIPG [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
  • Overall survival in patients with recurrent or refractory HGG or DIPG [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 57
Study Start Date: February 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 until the maximum tolerated dose (MTD) will be reached. 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.
Drug: Cabazitaxel (XRP6258)
Pharmaceutical form: Injection Route of administration: Intravenous
Other Name: Jevtana

Detailed Description:

The study duration will include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The patients may continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

  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 ≥1.0x109/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 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 1 before entering this 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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01751308

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Arizona
Investigational Site Number 840009 Recruiting
Phoenix, Arizona, United States, 85006
United States, Colorado
Investigational Site Number 840007 Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Investigational Site Number 840005 Recruiting
Orlando, Florida, United States, 32806
United States, Maryland
Investigational Site Number 840010 Recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Investigational Site Number 840002 Recruiting
Boston, Massachusetts, United States, 02115
United States, Missouri
Investigational Site Number 840004 Recruiting
Kansas City, Missouri, United States, 64108
United States, New York
Investigational Site Number 840003 Recruiting
New York, New York, United States, 10021
United States, Pennsylvania
Investigational Site Number 840001 Recruiting
Hershey, Pennsylvania, United States, 17033
United States, Texas
Investigational Site Number 840006 Recruiting
Houston, Texas, United States, 77030
United States, Washington
Investigational Site Number 840008 Recruiting
Seattle, Washington, United States, 98105
Canada
Investigational Site Number 124002 Recruiting
Calgary, Canada, T3B 6A8
Investigational Site Number 124001 Recruiting
Toronto, Canada, M5G 1X8
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01751308     History of Changes
Other Study ID Numbers: TED12689, U1111-1128-5704
Study First Received: December 13, 2012
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on April 15, 2014