CompletedNCT00939770Updated Jun 9, 2020Results posted

Crizotinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

A Phase 1/2 interventional study of Crizotinib and Laboratory Biomarker Analysis in Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Malignant Solid Neoplasm and Recurrent Neuroblastoma, sponsored by Children's Oncology Group. Completed at 28 sites in 2 countries. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2020-06-09.

Sponsored by Children's Oncology Group · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 122
Ages: 1 Year to 21 Years
Sex: All

Study 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)

Read the detailed description

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.

Conditions studied

Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Malignant Solid Neoplasm
Recurrent Neuroblastoma
Refractory Anaplastic Large Cell Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Neuroblastoma

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In context

Lymphoma, Large-Cell, Anaplastic

228 studies on the registry are indexed under Lymphoma, Large-Cell, Anaplastic; 27 are open to participants now.

This study's enrollment of 122 is above the median of 40 across 195 interventional studies indexed under Lymphoma, Large-Cell, Anaplastic.

Browse Lymphoma, Large-Cell, Anaplastic studies →

Lead sponsor

Children's Oncology Group is the lead sponsor of 447 studies on the registry; 35 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 1 Year to 21 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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:
  - Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan or X-ray obtained within 2 weeks prior to study enrollment
  - Evaluable tumor by meta-iodobenzyl guanidine I 123 (MIBG) scan and/or bone marrow involvement with tumor cells seen on routine morphology
- Phase 2 (Part C): Patients must have proven ALK+ disease with either measurable or evaluable disease
Performance level: Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =\< 16 years of age); Note: patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy:
- Myelosuppressive chemotherapy:
  - Solid tumors: Patients with solid tumors must not have received chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
  - Lymphoma: Patients with lymphoma who relapse during standard maintenance therapy are eligible at time of relapse; for patients with ALCL who relapse while they are receiving cytotoxic therapy, at least 14 days must have elapsed since the completion of cytotoxic therapy; Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of Crizotinib
At least 7 days since the completion of therapy with a growth factor
At least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody
>= 2 weeks (wks) for local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 6 months must have elapsed if prior total body irradiation (TBI), craniospinal XRT or >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation
Bone marrow/stem cell transplant or infusion without TBI:
- Part A1 or Part C: No evidence of active graft vs host disease and >= 3 months must have elapsed since stem cell transplant or infusion
- Part A2, Part A3, or Part B: No evidence of active graft vs host disease and >= 6 weeks must have elapsed since stem cell transplant or infusion
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Patients must not have received prior therapy with Crizotinib
Patients on Part A1 or Part C of the study:
- For patients with solid tumors or ALCL without bone marrow involvement:
  - Peripheral absolute neutrophil count (ANC) >= 1,000/mm\^3
  - Platelet count >= 75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  - Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
- Patients with known bone marrow metastatic disease:
  - Peripheral absolute neutrophil count (ANC) >= 750/mm\^3
  - Platelet count >= 25,000/mm\^3 (may receive platelet transfusions)
  - Hemoglobin >= 8.0 g/dL (may receive RBC transfusions)
  - Not known to be refractory to RBC or platelet transfusions Transfusions are permitted to meet both the platelet and hemoglobin criteria; Note: patients with known bone marrow metastatic disease are not evaluable for hematological toxicity for the purposes of dose escalation
Patients eligible for Part A2, Part A3, or Part B of the study must meet the hematologic criteria below for enrollment:
- Peripheral absolute neutrophil count (ANC) >= 750/mm\^3
- Platelet count >= 25,000/mm\^3 (may receive platelet transfusions)
- Hemoglobin >= 8.0 g/dL (may receive RBC transfusions)
- Not known to be refractory to red cell or platelet transfusions Transfusions are permitted to meet both the platelet and hemoglobin criteria
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
- 1 to \< 2 years: 0.6 mg/dL
- 2 to \< 6 years: 0.8 mg/dL
- 6 to \< 10 years: 1 mg/dL
- 10 to \< 13 years: 1.2 mg/dL
- 13 to \< 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
- >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =\< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
Serum albumin >= 2 g/dL
Corrected QT interval (QTc) =\< 480 msec
All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Patients taking the capsule formulation must be able to swallow capsules; feeding tube administration is allowed for patients receiving the oral solution (OS)

Exclusion criteria

Exclusion Criteria:

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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 122 participants (actual)

Study arms

Experimental
Treatment (crizotinib)
Patients receive crizotinib PO BID on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Crizotinib · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study · Other: Questionnaire Administration

Interventions

DrugCrizotinib
Given PO
Also known as: MET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori
OtherLaboratory Biomarker Analysis
Correlative studies
OtherPharmacological Study
Correlative studies
OtherQuestionnaire Administration
Ancillary studies

What researchers measure

Primary outcomes

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

Secondary outcomes

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

Results

Posted May 5, 2020

Participant flow

Participant flow — Overall Study
Milestone	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m2/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m2/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m2/Dose BID
Started	6	8	23	12	38	11	14	10
Completed	1	0	3	1	1	0	0	0
Not completed	5	8	20	11	37	11	14	10
Withdrew: Adverse event	1	1	0	0	6	2	1	1
Withdrew: Lack of efficacy	4	6	13	9	16	8	11	1
Withdrew: Lost to follow-up	0	0	0	0	1	0	0	0
Withdrew: Physician decision	0	0	2	0	7	1	0	6
Withdrew: Protocol violation	0	0	0	0	1	0	0	0
Withdrew: Withdrawal by subject	0	1	5	2	6	0	2	2

Outcome measures

PrimaryMaximum-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
Reported as:: Number · mg/m²/dose BID

Maximum-tolerated Dose and Recommended Phase 2 Dose of Crizotinib
mg/m²/dose BID	Part A
Maximum-tolerated Dose and Recommended Phase 2 Dose of Crizotinib	280

PrimaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants With Toxicities of Crizotinib
Participants	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1: Part A:PF-02341066 130 mg/m²/Dose BID	Phase 1: Part A:PF-02341066 165 mg/m²/Dose BID	Phase 1: Part A:PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A:PF-02341066 280 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m²/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	Phase 2:Part C: PF-02341066 280 mg/m2/Dose BID
Number of Participants With Toxicities of Crizotinib	6	7	23	11	38	11	14	10

PrimarySteady 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
Reported as:: Mean · ng/mL

Steady State C Max of Crizotinib
ng/mL	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6
Steady State C Max of Crizotinib	294 ± 0	601 ± 118	717 ± 201	972 ± 210

PrimarySteady 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
Reported as:: Mean · ng/mL

Steady State C Average of Crizotinib
ng/mL	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6
Steady State C Average of Crizotinib	246 ± 0	469 ± 114	582 ± 173	731 ± 228

PrimarySteady 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
Reported as:: Mean · ng•h/mL

Steady State AUC of Crizotinib
ng•h/mL	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6
Steady State AUC of Crizotinib	2950 ± 0	5630 ± 1370	6990 ± 2080	8770 ± 2740

PrimarySteady 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
Reported as:: Mean · mL/min/m2

Steady State Clearance of Crizotinib
mL/min/m2	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6
Steady State Clearance of Crizotinib	735 ± 0	652 ± 159	736 ± 255	731 ± 223

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants (Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma (ALCL))With Response to Crizotinib
Participants	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m2/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m2/Dose BID
Number of Participants (Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma (ALCL))With Response to Crizotinib	0	0	7	0	19	1

SecondaryNumber of Participants (Relapsed or Refractory Neuroblastoma or Anaplastic Large Cell Lymphoma (ALCL)) With Response to Crizotinib

Time frame:: Up to 8 years
Reported as:: Count of participants · Participants

Number of Participants (Relapsed or Refractory Neuroblastoma or Anaplastic Large Cell Lymphoma (ALCL)) With Response to Crizotinib
Participants	Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m2/Dose BID
Number of Participants (Relapsed or Refractory Neuroblastoma or Anaplastic Large Cell Lymphoma (ALCL)) With Response to Crizotinib	1	7

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants With Minimum Residual Disease (MRD)
Participants	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m2/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m2/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m2/Dose BID
Number of Participants With Minimum Residual Disease (MRD)	0	0	5	0	9	0	0	10

Adverse events

Collected over Up to 3 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	0/6 (0%)	3/6 (50%)	6/6 (100%)
Phase 1: Part A: PF-02341066 130 mg/m²/Dose BID	0/8 (0%)	6/8 (75%)	8/8 (100%)
Phase 1: Part A: PF-02341066 165 mg/m²/Dose BID	3/23 (13%)	18/23 (78.3%)	23/23 (100%)
Phase 1: Part A: PF-02341066 215 mg/m²/Dose BID	2/12 (16.7%)	10/12 (83.3%)	12/12 (100%)
Phase 1: Part A: PF-02341066 280 mg/m2/Dose BID	2/38 (5.3%)	33/38 (86.8%)	38/38 (100%)
Phase 1: Part A: PF-02341066 365 mg/m2/Dose BID	1/11 (9.1%)	11/11 (100%)	11/11 (100%)
Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	1/14 (7.1%)	13/14 (92.9%)	14/14 (100%)
Phase 2: Part C: PF-02341066 280 mg/m2/Dose BID	0/10 (0%)	10/10 (100%)	10/10 (100%)

Most frequent serious events

Showing 10 of 113

Most frequent serious events
Event	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m2/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m2/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m2/Dose BID
Neutrophil count decreasedInvestigations	2/6	3/8	10/23	6/12	18/38	7/11	10/14	10/10
AnemiaBlood and lymphatic system disorders	1/6	2/8	5/23	1/12	5/38	0/11	4/14	5/10
Lymphocyte count decreasedInvestigations	3/6	3/8	7/23	2/12	9/38	1/11	6/14	5/10
Platelet count decreasedInvestigations	2/6	2/8	3/23	1/12	7/38	0/11	4/14	5/10
White blood cell decreasedInvestigations	1/6	2/8	3/23	3/12	9/38	1/11	4/14	5/10
Febrile neutropeniaBlood and lymphatic system disorders	2/6	1/8	2/23	0/12	2/38	0/11	1/14	1/10
AnorexiaMetabolism and nutrition disorders	0/6	2/8	4/23	0/12	1/38	0/11	2/14	0/10
Tumor painNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/6	2/8	0/23	0/12	1/38	0/11	1/14	0/10
Infections and infestations - Other, specifyInfections and infestations	0/6	0/8	5/23	1/12	2/38	0/11	1/14	1/10
Hearing impairedEar and labyrinth disorders	0/6	1/8	1/23	1/12	3/38	1/11	3/14	0/10

Most frequent other events

Showing 10 of 297

Most frequent other events
Event	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m2/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m2/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m2/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m2/Dose BID
Alanine aminotransferase increasedInvestigations	6/6	3/8	20/23	11/12	33/38	8/11	12/14	9/10
AnemiaBlood and lymphatic system disorders	6/6	6/8	20/23	8/12	33/38	11/11	13/14	7/10
Aspartate aminotransferase increasedInvestigations	6/6	4/8	21/23	11/12	33/38	11/11	14/14	8/10
DiarrheaGastrointestinal disorders	3/6	3/8	15/23	6/12	25/38	9/11	11/14	10/10
VomitingGastrointestinal disorders	4/6	2/8	20/23	9/12	29/38	11/11	13/14	10/10
NauseaGastrointestinal disorders	5/6	6/8	21/23	9/12	31/38	9/11	10/14	8/10
White blood cell decreasedInvestigations	4/6	3/8	20/23	7/12	31/38	10/11	12/14	8/10
CoughRespiratory, thoracic and mediastinal disorders	5/6	2/8	16/23	5/12	24/38	3/11	7/14	4/10
Creatinine increasedInvestigations	5/6	2/8	15/23	5/12	16/38	6/11	9/14	3/10
HypoalbuminemiaMetabolism and nutrition disorders	5/6	4/8	18/23	5/12	30/38	5/11	11/14	8/10

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m²/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m²/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m²/Dose BID	Total
<=18 years	6	7	21	11	34	10	14	10	113
Between 18 and 65 years	0	1	2	1	4	1	0	0	9
>=65 years	0	0	0	0	0	0	0	0	0

Age, Continuous
Age, Continuous(years)	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m²/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m²/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m²/Dose BID	Total
Median	8.5 (5 to 12)	12 (6 to 20)	8 (1 to 21)	11.5 (3 to 20)	9 (1 to 21)	10 (2 to 20)	5.5 (3 to 14)	9.5 (6 to 15)	9 (1 to 21)

Sex: Female, Male
Sex: Female, Male(Participants)	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m²/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m²/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m²/Dose BID	Total
Female	2	3	9	6	25	5	8	2	60
Male	4	5	14	6	13	6	6	8	62

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m²/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m²/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m²/Dose BID	Total
Hispanic or Latino	0	0	1	2	6	2	1	1	13
Not Hispanic or Latino	5	8	21	7	28	8	13	8	98
Unknown or Not Reported	1	0	1	3	4	1	0	1	11

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase 1: Part A: PF-02341066 100 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 130 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 165 mg/m²/Dose BID	Phase 1:Part A: PF-02341066 215 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 280 mg/m²/Dose BID	Phase 1: Part A: PF-02341066 365 mg/m²/Dose BID	Phase 2: Part B: PF-02341066 280 mg/m²/Dose BID	Phase 2: Part C: PF-02341066 280 mg/m²/Dose BID	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0
Asian	0	1	1	0	1	1	1	1	6
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0
Black or African American	1	0	0	0	5	1	1	3	11
White	5	6	19	8	25	8	12	4	87
More than one race	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	1	3	4	7	1	0	2	18

Study locations

28 sites

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

References and documents

Publications

Bartlett JA, Culver N, Santangelo M, Prpich A, Long E, Sagawa K, Shanker R, Xu H, Wilner K. Development of a Taste-Masked, Dose-Flexible, Multiparticulate Pediatric Dosage Form: Case Study of Crizotinib, a Challenging Pediatric Formulation. Pharmaceut Med. 2026 May;40(3):193-207. doi: 10.1007/s40290-026-00604-2. Epub 2026 Apr 1. PubMed 41920422 ↗
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. PubMed 33568345 ↗
Balis 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. PubMed 28032129 ↗
Mosse 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. PubMed 23598171 ↗

Study documents

Protocol, analysis plan and consent form · Jul 27, 2017

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 9, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00939770
Lead sponsor: Children's Oncology Group
Collaborators: National Cancer Institute (NCI), Pfizer
Responsible party: Sponsor
First posted: Jul 15, 2009
Start date: Sep 21, 2009
Primary completion: Dec 31, 2018
Completion: Dec 31, 2018
Results posted: May 5, 2020
Last update: Jun 9, 2020

Study contacts

Yael P Mosse

principal investigator · COG Phase I Consortium

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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