Crizotinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
A Phase 1/2 Study of Crizotinib, an Oral Small Molecule Inhibitor of Anaplastic Lymphoma Kinase (ALK) and C-Met, in Children With Relapsed/Refractory Solid Tumors and Anaplastic Large Cell Lymphoma
6 other identifiers
interventional
122
2 countries
28
Brief Summary
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2009
Longer than P75 for phase_1
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 14, 2009
CompletedFirst Posted
Study publicly available on registry
July 15, 2009
CompletedStudy Start
First participant enrolled
September 21, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2018
CompletedResults Posted
Study results publicly available
May 5, 2020
CompletedJune 9, 2020
January 1, 2020
9.3 years
July 14, 2009
January 31, 2020
June 4, 2020
Conditions
Outcome Measures
Primary Outcomes (6)
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.
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.
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.
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.
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.
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.
Cycle 1 (day 15-28) pre-dose, 1, 2, 4, 6-8 hour post-dose
Secondary Outcomes (3)
Number of Participants (Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma (ALCL))With Response to Crizotinib
Up to 8 years
Number of Participants (Relapsed or Refractory Neuroblastoma or Anaplastic Large Cell Lymphoma (ALCL)) With Response to Crizotinib
Up to 8 years
Number of Participants With Minimum Residual Disease (MRD)
Up to 8 years
Study Arms (1)
Treatment (crizotinib)
EXPERIMENTALPatients receive crizotinib PO BID on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Eligibility Criteria
You may qualify if:
- Patients receiving the formulated capsules must have a body surface area (BSA) \>= 0.63 m\^2 at the time of study enrollment
- Patients must have had histologic verification of malignancy at original diagnosis or relapse
- \* Phase 1 (Part A1) - COMPLETE: Patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma (excluding patients with primary or metastatic central nervous system \[CNS\] tumors or patients with primary cutaneous ALCL)
- \* Phase 1 (Part A2) - COMPLETE: Patients with confirmed ALK fusion proteins, ALK mutations, ALK amplification (defined as greater than 4-fold increase in the ALK signal number as compared to reference signal number on chromosome 2q arm) or MET proto-oncogene, receptor tyrosine kinase (MET) mutation or amplification; testing to confirm the presence of ALK fusion proteins, ALK mutations, ALK amplification or evidence of MET mutation or amplification for eligibility purposes must be performed as a Clinical Laboratory Improvement Act (CLIA)-certified assay; ALK immunohistochemistry can be used as a surrogate for fluorescent in situ hybridization (FISH) for patients with inflammatory myofibroblastic tumors (IMT) or ALCL
- \*\* Note: Evidence for MET mutation or amplification is defined as:
- Positive for c-Met amplification by FISH; or
- Positive for known c-Met kinase domain activating mutations including V1110L, H1112L, H1112Y, H1124D, M1149T, T1191I, V1206L, L1213V, V1238I, M1268T, P1009S, T1010I, R988C, V941L, but excluding Y1248C, Y1248H, Y1248D, and Y1253D; or
- Chromosomal translocations that lead to altered transcriptional regulation of c-Met and/or hepatocyte growth factor (HGF) including metastatic alveolar soft part sarcoma, clear cell sarcoma, rhabdomyosarcoma, or translocation associated renal cell carcinoma)
- \* Phase 1 (Part A3) - COMPLETE: Patients with relapsed or refractory neuroblastoma, with or without bone marrow involvement, who are not eligible for Part A1 or A2 or cannot enroll on Part A1 because of stratum suspension or lack of available slots (these patients will be enrolled at one dose level below the dose level at which patients on Part A1 are actively enrolling)
- \* Phase 2 (Part B): Patients with ALK+ relapsed or refractory neuroblastoma
- \* Phase 2 (Part C): Patients with ALK+ relapsed or refractory ALCL (excluding patients with primary cutaneous ALCL)
- \* Phase 2 (Part A2): Patients with diagnoses other than neuroblastoma or ALCL with confirmed ALK fusion proteins, ALK mutations, ALK amplification (defined as greater than 4-fold increase in the ALK signal number as compared to reference signal number on chromosome 2q arm) or MET mutation or amplification; testing to confirm the presence of ALK fusion proteins, ALK mutations, ALK amplification or evidence of MET mutation or amplification for eligibility purposes must be performed as a CLIA-certified assay; ALK immunohistochemistry can be used as a surrogate for FISH for patients with IMT
- Disease status:
- Phase 1 (Part A): Patients must have either measurable and/or evaluable disease
- Phase 2 (Part B): Patients with neuroblastoma must have proven ALK+ disease with either measurable and/or evaluable disease as indicated below:
- +45 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents, with the exception of hydroxyurea for patients with ALCL, are not eligible
- As Crizotinib is an inhibitor of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
- Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to, ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
- Patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John's wort are not eligible; the topical use of these medications (if applicable) is allowed
- Patients with known interstitial fibrosis or interstitial lung disease are not eligible
- Patients with a known history of myocardial infarction or cerebrovascular accident are not eligible
- Patients with central nervous system (CNS) tumors or known CNS metastases are not eligible; patients with a history of CNS metastases that have been surgically resected are eligible only if the baseline evaluation shows no evidence of current CNS metastases; patients with any evidence of CNS metastases on baseline evaluation are not eligible, regardless of whether the lesions have been previously treated and/or appear stable
- Patients who have an uncontrolled infection are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
- Pfizercollaborator
Study Sites (28)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (3)
Foster JH, Voss SD, Hall DC, Minard CG, Balis FM, Wilner K, Berg SL, Fox E, Adamson PC, Blaney SM, Weigel BJ, Mosse YP. Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Clin Cancer Res. 2021 Jul 1;27(13):3543-3548. doi: 10.1158/1078-0432.CCR-20-4224. Epub 2021 Feb 10.
PMID: 33568345DERIVEDBalis FM, Thompson PA, Mosse YP, Blaney SM, Minard CG, Weigel BJ, Fox E. First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children's Oncology Group Phase 1/Pilot Consortium. Cancer Chemother Pharmacol. 2017 Jan;79(1):181-187. doi: 10.1007/s00280-016-3220-6. Epub 2016 Dec 28.
PMID: 28032129DERIVEDMosse YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, Rolland D, Balis FM, Maris JM, Weigel BJ, Ingle AM, Ahern C, Adamson PC, Blaney SM. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol. 2013 May;14(6):472-80. doi: 10.1016/S1470-2045(13)70095-0. Epub 2013 Apr 16.
PMID: 23598171DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Yael P Mosse
COG Phase I Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 14, 2009
First Posted
July 15, 2009
Study Start
September 21, 2009
Primary Completion
December 31, 2018
Study Completion
December 31, 2018
Last Updated
June 9, 2020
Results First Posted
May 5, 2020
Record last verified: 2020-01