Clinical trial NCT00658658: Panitumumab in Children With Solid Tumors
Official title: A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Panitumumab in Children With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Epidermal Growth Factor
Pediatric
Solid Tumors
Panitumumab
Dose Limiting Toxicity
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-04-15
Enrollment: 31
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to evaluate the safety and pharmacokinetics of up to 3 different dose schedules of panitumumab in pediatric patients with solid tumors.

Detailed description: This is an open-label, multi-center, single arm, dose-ranging, clinical study. Panitumumab will be administered by intravenous infusion to 4-6 patients per cohort. Three planned cohorts, stratified by age, will be studied at 100% of the recommended panitumumab dose for each treatment schedule as defined in adults. Enrollment will start with a 2.5 mg/kg once weekly administration to the 12 to \< 18 year old patients. Upon demonstration of sufficient safety additional cohorts will open; a 2.5 mg/kg once weekly administration to the 1 to \< 12 year old patients and a 6.0 mg/kg once every two weeks to the 12 to \< 18 year old patients. The decision to advance to the next cohort will be based on observance of ≤ 33% incidence of a dose limiting toxicity during the evaluation period. Subsequent cohorts of 6.0 mg/kg once every two weeks to the 1 to \< 12 year old patients and 9.0 mg/kg once every three weeks to both age groups will open once sufficient safety in each cohort is determined. Participants may stay on study treatment until disease progression.

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.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: 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.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose date to end of study date. The median duration of study was 47 days.
measure: Maximum Observed Concentration (Cmax) of Panitumumab
timeFrame: 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).
measure: Minimum Observed Concentration (Cmin) of Panitumumab
timeFrame: 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).
measure: Area Under the Concentration-time Curve During the Dosing Interval (AUC0-tau) for Panitumumab
timeFrame: 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).
measure: Half-life (t1/2) for the Terminal Phase (First Dose) or Dosing Interval (Third Dose) of Panitumumab
timeFrame: 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).
measure: Serum Clearance (CL) of Panitumumab
timeFrame: 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: Number of Participants Who Developed Antibodies to Panitumumab
timeFrame: Before panitumumab administration on Day 1, Day 43, Day 169 and 30 days after last dose for all cohorts.
measure: Percentage of Participants With an Objective Response
timeFrame: Tumor response was assessed every 8 weeks through week 48 and every 3 months thereafter until disease progression or end of study. The data cut-off for the analysis was 17 June 2015; median duration of study was 47 days.
measure: Percentage of Participants With Disease Control
timeFrame: Tumor response was assessed every 8 weeks through week 48 and every 3 months thereafter until disease progression or end of study. The data cut-off for the analysis was 17 June 2015; median duration of study was 47 days.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: