Panitumumab in Children With Solid Tumors

NCT00658658 | Completed Phase 1 Results

• 2 other identifiers: 200502522014-005190-36
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 11

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.

Conditions

Solid Tumors

Keywords

Epidermal Growth Factor; Pediatric; Solid Tumors; Panitumumab; Dose Limiting Toxicity

Outcome Measures

Primary Outcomes (7)

• 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).

• Minimum Observed Concentration (Cmin) of Panitumumab

  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).

• Area Under the Concentration-time Curve During the Dosing Interval (AUC0-tau) for Panitumumab

  The area under the serum concentration-time curve from time zero to the end of the dosing interval (AUCtau), estimated using the linear trapezoidal method.

  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).

• Half-life (t1/2) for the Terminal Phase (First Dose) or Dosing Interval (Third Dose) of Panitumumab

  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).

• Serum Clearance (CL) of Panitumumab

  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 (3)

• Number of Participants Who Developed Antibodies to Panitumumab

  Before panitumumab administration on Day 1, Day 43, Day 169 and 30 days after last dose for all cohorts.

• Percentage of Participants With an Objective Response

  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.

• Percentage of Participants With Disease Control

  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.

Study Arms (1)

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

Interventions

Panitumumab BIOLOGICAL

Panitumumab administered by intravenous infusion

Also known as: Vectibix

Panitumumab

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parents or legal guardian signed-written informed consent
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (11)

Research Site

Los Angeles, California, 90027, United States

Location

Research Site

San Francisco, California, 94143, United States

Location

Research Site

Washington D.C., District of Columbia, 20010, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Minneapolis, Minnesota, 55455, United States

Location

Research Site

Kansas City, Missouri, 64108, United States

Location

Research Site

New York, New York, 10021, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Portland, Oregon, 97239-3098, United States

Location

Research Site

Nashville, Tennessee, 37232, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

Panitumumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2008
• First Posted: April 15, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 18, 2016
• Results First Posted: May 18, 2016

Record last verified: 2016-04

Locations

US (11)