Panitumumab in Children With Solid Tumors | NCT00658658

NCT00658658

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2014-005190-36	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
Panitumumab	Experimental	Participants received panitumumab at planned doses ranging from 2.5 mg/kg weekly (QW) to 9.0 mg/kg every 3 weeks (Q3W) until the patient experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.	Biological: Panitumumab

Name	Type	Description	Arm Group Labels	Other Names
Panitumumab	Biological	Panitumumab administered by intravenous infusion	Panitumumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs)	Any panitumumab related grade 3 or 4 hematologic or non-hematologic toxicity (graded according to the modified Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria) was considered a DLT with the exception of alopecia and fatigue. Hypomagnesemia, nausea, diarrhea, vomiting, and skin or nail toxicities constituted a DLT only of the following occured: • Grade 3 or 4 hypomagnesemia that persisted for at least 5 days despite maximal magnesium replacement; • Grade 3 or 4 diarrhea, nausea, or vomiting that persisted for at least 5 days despite maximum supportive therapy; • Grade 4 skin or nail toxicity.	28 days from initial administration of panitumumab for the 2.5 and 6 mg/kg cohorts and 21 days from first administration for the 9 mg/kg cohort.
Number of Participants With Adverse Events (AEs)	A serious adverse event is defined as an AE that: • is fatal; • is life threatening; • requires in-patient hospitalization or prolongation of existing hospitalization; • results in persistent or significant disability/incapacity; • is a congenital anomaly/birth defect; • other significant medical hazard. The investigator assessed whether adverse events were related to panitumumab. The severity of adverse events was based on CTCAE version 3 (with the exception of skin- or nail-related toxicities which were graded using the CTCAE version 3.0 with modifications), according to the following: Grade 1 = Mild (aware of sign or symptom, but easily tolerated); Grade 2 = Moderate (discomfort enough to cause interference with usual activity); Grade 3 = Severe (incapacitating with inability to work or do usual activity); Grade 4 = Life-threatening or disabling; Grade 5 = Fatal.	From first dose date to end of study date. The median duration of study was 47 days.
Maximum Observed Concentration (Cmax) of Panitumumab	Panitumumab serum concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 400 pg/mL. Concentrations below the LLOQ were set to zero.	First dose (Day 1) and third dose (Day 15/29/43 for the QW, Q2W and Q3W cohorts respectively). Samples were collected over the dosing interval for each treatment cohort (7, 14 or 21 days for QW, Q2W and Q3W cohorts respectively).

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Developed Antibodies to Panitumumab	Three validated assays were used to detect the presence of anti-panitumumab antibodies. Two screening immunoassays, an acid-dissociation enzyme-linked immunosorbent assay (ELISA) and a Biacore-based biosensor assay, were used to detect antibodies capable of binding to panitumumab. All samples confirmed to be positive by drug specificity in either screening immunoassay were further tested for neutralizing antibodies in a cell-based epidermal growth factor receptor (EGFR) phosphorylation bioassay. The number of participants who developed antibodies to panitumumab is the number of participants with a non-positive (including missing) antibody result at baseline and a positive antibody result at any post-baseline time point.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Parents or legal guardian signed-written informed consent
1 to < 18 years of age
Histologically or cytologically confirmed solid tumor that has recurred after standard therapy, or for which there is no standard therapy. Subjects with brainstem glioma DO NOT need histologic proof of the diagnosis.
Paraffin-embedded tumor tissue from primary tumor or metastasis for determination of epidermal growth factor receptor expression and biomarker testing
Central nervous system tumors are allowed
Presence of measurable or non-measurable disease.
Life expectancy of ≥ 12 weeks.
Performance status: Karnofsky ≥ 60% for 12 to <18 years of age; Lansky play scale ≥ 60% for 1 to < 12 years of age.
Adequate hematologic function.
Adequate renal function.
Adequate hepatic function.
Magnesium ≥ lower limit of normal (LLN)
Adequate pulmonary function
All previous therapy-related toxicities must have resolved or return to baseline.

Exclusion Criteria:

Diagnosis of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease or other hematologic malignancy.
Any prior allogeneic transplant.
Prior autologous bone marrow or peripheral stem cell transplant less than 3 months prior to enrollment.
Substantial radiotherapy to the bone marrow within 6 weeks prior to enrollment.
Prior use of any monoclonal antibodies directly targeting the epidermal growth factor receptor (EGFr). Subjects who have received prior tyrosine kinase inhibitors such as gefitinib or erlotinib are eligible.
Immunotherapy, radiotherapy, or chemotherapy ≤ 2 weeks prior to enrollment. (≤ 6 weeks for nitrosoureas, mitomycin-C, and liposomal doxorubicin, and ≤ 6 weeks from prior antibody therapy).
Requirement to receive concurrent chemotherapy, immunotherapy, radiotherapy (except for pain control) or any other investigational drug while on this study.
Prior seizures < 3 months prior to enrollment. Subjects with a history of seizure disorders ≥ 3 months prior to enrollment must be seizure free and on stable anticonvulsant medication(s) for ≥ 3 months prior to enrollment).
Presence of a serious uncontrolled medical disorder.
Dementia, altered mental status, or any other medical condition or disorder that would prohibit the understanding or rendering of assent (if applicable), or ability to comply with study procedures.
Major surgery ≤ 28 days prior to enrollment.
Known or suspected history of interstitial lung disease.
Active inflammatory bowel disease or other bowel disease causing chronic diarrhea.
Known positive test for human immunodeficiency virus infection, hepatitis C virus, acute or chronic hepatitis B infection, or any co-morbid disease that would increase risk of toxicity.
Females of childbearing potential not using adequate contraception precautions for the duration of the study treatment and for 2 months after the last administration of investigational product.
Pregnant or breast-feeding, or planning to become pregnant during study treatment and within 2 months after the last administration of investigational product.
Received investigational therapy or procedure ≤ 30 days prior to enrollment.

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Los Angeles	California	90027	United States
Research Site

Label	URL
AmgenTrials clinical trials website	View source

Arm/Group Information

ID	Title	Description
FG000	Age 12-17: 2.5 mg/kg QW	Participants aged 12 to 17 years received panitumumab 2.5 mg/kg administered by intravenous (IV) infusion weekly (QW) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
FG001	Age 12-17: 6 mg/kg Q2W	Participants aged 12 to 17 years received panitumumab 6 mg/kg administered by IV infusion every 2 weeks (Q2W) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
FG002	Age 12-17: 9 mg/kg Q3W	Participants aged 12 to 17 years received panitumumab 9 mg/kg administered by IV infusion every 3 weeks (Q3W) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
FG003	Age 1-11: 2.5 mg/kg QW	Participants aged 1 to 11 years received panitumumab 2.5 mg/kg administered by IV infusion QW until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
FG004	Age 1-11: 6 mg/kg Q2W	Participants aged 1 to 11 years received panitumumab 6 mg/kg administered by IV infusion Q2W until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Age 12-17: 2.5 mg/kg QW	Participants aged 12 to 17 years received panitumumab 2.5 mg/kg administered by intravenous (IV) infusion weekly (QW) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
BG001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose-limiting Toxicities (DLTs)

Any panitumumab related grade 3 or 4 hematologic or non-hematologic toxicity (graded according to the modified Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria) was considered a DLT with the exception of alopecia and fatigue. Hypomagnesemia, nausea, diarrhea, vomiting, and skin or nail toxicities constituted a DLT only of the following occured: • Grade 3 or 4 hypomagnesemia that persisted for at least 5 days despite maximal magnesium replacement; • Grade 3 or 4 diarrhea, nausea, or vomiting that persisted for at least 5 days despite maximum supportive therapy; • Grade 4 skin or nail toxicity.

DLT Analysis Set (all participants who received at least 1 dose of panitumumab and were evaluated for DLTs and completed at least 28 days (for the 2.5 and 6 mg/kg cohorts) or 21 days (for 9 mg/kg cohort) of therapy unless due to a DLT)

Posted

Number

participants

28 days from initial administration of panitumumab for the 2.5 and 6 mg/kg cohorts and 21 days from first administration for the 9 mg/kg cohort.

ID	Title	Description

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Age 12-17: 2.5 mg/kg QW	Participants aged 12 to 17 years received panitumumab 2.5 mg/kg administered by intravenous (IV) infusion weekly (QW) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

OG000	Age 12-17: 2.5 mg/kg QW	Participants aged 12 to 17 years received panitumumab 2.5 mg/kg administered by intravenous (IV) infusion weekly (QW) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
OG001	Age 12-17: 6 mg/kg Q2W	Participants aged 12 to 17 years received panitumumab 6 mg/kg administered by IV infusion every 2 weeks (Q2W) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
OG002	Age 12-17: 9 mg/kg Q3W	Participants aged 12 to 17 years received panitumumab 9 mg/kg administered by IV infusion every 3 weeks (Q3W) until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
OG003	Age 1-11: 2.5 mg/kg QW	Participants aged 1 to 11 years received panitumumab 2.5 mg/kg administered by IV infusion QW until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.
OG004	Age 1-11: 6 mg/kg Q2W	Participants aged 1 to 11 years received panitumumab 6 mg/kg administered by IV infusion Q2W until the participant experienced disease progression, was unable to tolerate study drug, withdrew consent, or other reasons that warranted removal from the study.