E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065143 |
E.1.2 | Term | Malignant solid tumour |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and pharmacokinetics (PK) of up to 3 different dose schedules of panitumumab in pediatric subjects with solid tumors. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the incidence of human anti-panitumumab antibody
(HAPA) formation and to preliminarily determine if there is evidence of anti-tumor activity of panitumumab in this patient population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• All parents or legal guardians must provide voluntary, signed-written informed consent before any study-specific procedure is conducted. In addition to providing written informed consent, the assent of the child (if applicable) must also be obtained in accordance with the institutional review board (IRB)/independent ethics committee before
any study-specific procedure is conducted.
• 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.
• Central nervous system (CNS) tumors (primary or metastatic) are allowed.
Note:
Subjects who have received prior radiotherapy for CNS metastases must have a minimum of 4 weeks elapsed since last dose of radiotherapy and be considered medically stable and must be on a stable dose of corticosteroids for a minimum of 2 weeks prior to participation in the study.
• Paraffin-embedded tumor tissue from primary tumor or metastasis for determination of epidermal growth factor receptor (EGFr) expression and biomarker testing (not required for brainstem gliomas, if not available)
• Presence of measurable or non-measurable disease
• Life expectancy of ≥ 12 weeks
• Performance status: Karnofsky ≥ 60% for 12 to < 18 years of age (Appendix M); Lansky play scale ≥ 60% for children 1 to < 12 years of age (Appendix N)
• Adequate hematologic function, as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 75 x 109/L
- Hemoglobin ≥ 9 g/dL
• Adequate renal function as follows:
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age
• Adequate hepatic function, as follows:
− Aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 X ULN if liver metastases)
− Alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 X ULN if liver metastases)
− Total bilirubin ≤ 1.5 X ULN
• Magnesium ≥ lower limit of normal
• Adequate pulmonary function, as follows:
− Resting O2 saturation on room air ≥ 92% by pulse oximetry
• All previous therapy-related toxicities must have resolved or returned to baseline |
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E.4 | Principal 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 (or within 6 months prior to enrollment if prior radiotherapy to the craniospinal axis or to at least 59% of the pelvis was received; within 2 weeks prior to enrollment if local palliative radiotherapy was received)
• Prior use of any monoclonal antibodies directly targeting the EGFr. Subjects who have received prior tyrosine kinase inhibitors such as gefitinib (Iressa) or erlotinib (Tarceva) 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 (eg, pneumonitis or pulmonary fibrosis)
• Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as ≥ CTC grade 2 [CTCAE version 3.0])
• 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety and Tolerability: subject and cohort incidence of grade 3 and 4 adverse events (AEs) including DLTs, serious adverse events (SAEs), and events requiring the discontinuation of study drug
• Safety: subject incidence of clinically significant laboratory changes, clinically significant changes in vital signs, and all AEs
• PK parameters: AUC, Cmin and Cmax, t1/2, CL, and V
The results of this study will be used to define a safe dose schedule to be tested in a Phase 2 study in this population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
There are no set timepoints for the evaluation of the endpoints, as the study is cohort driven. |
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E.5.2 | Secondary end point(s) |
• Immunogenicity: incidence of human anti-panitumumab antibody formation
• Efficacy: tumor response. These endpoints will pertain only to subjects with measurable disease at baseline. Tumor response will be assessed per the investigator (ie, no central review) using a modification of the RECIST criteria version 1.0 (Appendix L). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
There are no set timepoints for the evaluation of the endpoints, as the study is cohort driven. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Evaluation of pharmacokinetics in children with solid tumors |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as completion of the 30 days ± 3 days safety visit after the last dose of panitumumab after the last subject is enrolled. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |