This phase 1/2 trial the studies side effects and best dose of crizotinib and to see how well it works in treating young patients with solid tumors or anaplastic large cell lymphoma that has returned after a period of improvement or does not respond to treatment. Crizotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. (Phase 1 completed 2/15/13)
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and recommend a Phase 2 dose of Crizotinib administered orally twice daily to children with relapsed/refractory solid tumors and anaplastic large cell lymphoma (ALCL). (completed 2/15/13) II. To define and describe the toxicities of Crizotinib administered on this schedule. III. To characterize the pharmacokinetics of Crizotinib in children with refractory cancer. SECONDARY OBJECTIVES: I. To preliminarily define the anti-tumor activity of Crizotinib within the confines of a Phase 1 study. (completed 2/15/13) II. To obtain initial Phase 2 data on the anti-tumor activity of Crizotinib in children with relapsed/refractory neuroblastoma and ALCL. III. To preliminarily examine the relationship between anaplastic lymphoma kinase (ALK) status (e.g, the presence of a mutation, duplication, amplification, and/or translocation) in patients with neuroblastoma (NB) or ALCL and response to Crizotinib. IV. To preliminarily examine the relationship between minimal residual disease (MRD) status and clinical response to Crizotinib in patients with ALCL. V. To use a questionnaire to gather preliminary information on the palatability of the oral solution formulation of Crizotinib. VI. To evaluate for potential alterations in bone growth in pediatric patients. OUTLINE: This is a phase 1 dose-escalation study (completed 2/15/13) followed by a phase 2 study. Patients receive crizotinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
122
Children's Hospital of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Maximum-tolerated Dose and Recommended Phase 2 Dose of Crizotinib
The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for adverse event (AE) reporting. The MTD/RP2D is defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity.
Time frame: 28 days
Number of Participants With Toxicities of Crizotinib
The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for AE reporting.
Time frame: Up to 30 days post-treatment
Steady State C Max of Crizotinib
Mean with standard deviation of peak of serum concentration curve at steady state by dose level.
Time frame: Cycle 1 (day 15- 28) pre-dose, 1, 2,4, 6-8 hours post dose
Steady State C Average of Crizotinib
Mean with standard deviation of average serum concentration curve at steady state by dose level.
Time frame: Cycle 1 (day 15-28) pre-dose, 1, 2, 4, 6-8 hours post-dose
Steady State AUC of Crizotinib
Mean with standard deviation of area under the serum concentration curve at steady state by dose level.
Time frame: Cycle 1 (day 15-28) pre-dose, 1, 2, 4, 6-8 hours post-dose
Steady State Clearance of Crizotinib
Mean with standard deviation of the elimination of crizotinib at steady state by dose level.
Time frame: Cycle 1 (day 15-28) pre-dose, 1, 2, 4, 6-8 hour post-dose
Number of Participants (Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma (ALCL))With Response to Crizotinib
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 8 years
Number of Participants (Relapsed or Refractory Neuroblastoma or Anaplastic Large Cell Lymphoma (ALCL)) With Response to Crizotinib
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 8 years
Number of Participants With Minimum Residual Disease (MRD)
MRD status will be reported descriptively. The relationship between MRD status and clinical response to treatment will be examined in children with ALCL.
Time frame: Up to 8 years
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Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
...and 18 more locations