- freely available
Children 2015, 2(2), 198-210; https://doi.org/10.3390/children2020198
1. Clinical Trials
- Scientific curiosity vs. the rights and interests of the patients/healthy volunteers involved in clinical research
- A clinical trial can provide evidence whether a given treatment is working or not. This will have a deep financial impact on a sponsoring company. Reporting a positive outcome of a new treatment can also have a significant career impact for a leading clinical investigator [6,7]. There are temptations for both to misrepresent, omit, twist or even falsify data.
- Randomized double-blind regulatory clinical trials have today a high weight in regulatory authorities’ decisions to approve new drugs. Clinicians will then prescribe them. Individual experience and learning is to some degree superseded by a complex system that includes approval of medicines by regulatory authorities and scientific agreement through literature, treatment guidelines, consensus papers, and more.
- To summarize, clinical trials play a key role in advancing medical science. However, clinical trials can also put patients into situations that can deeply affect their health and well-being, and key decisions are not immediately made by the treating physicians only. A thorough balance is required to allow on one side, progress in science, clinical understanding and therapeutic interventions, and on the other side, prevent damage to the individual patient, which in consequence, will damage the societal acceptance of clinical trials.
2. Clinical Trials in Children
3. Ethics Committees/IRBs
4. Modern Drugs and Children
5. Reflections on Pharmaceutical Pediatric Legislation
6. Ethics Committees/IRBs and Clinical Trials in Children
7. Ambitions of the European Medicines Agency (EMA) and its Paediatric Committee (PDCO)
|Study ID||Study Title||Sponsor||Intervention||Patient Age||Centers|
|NCT00743496||A Phase I Trial Of The Humanized Anti-GD2 Antibody In Children And Adolescents With Neuroblastoma, Osteosarcoma, Ewing Sarcoma and Melanoma||St. Jude Children’s Research Hospital||Anti-GD2 antibody||Up to 21 years||1 US Center|
|NCT01696045||Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage lV Malignant Melanoma||Bristol-Myers Squibb||Ipilimumab||12–17 years||32 centers USA, UK, Australia, Mexico, Belgium, Denmark, France, Germany|
|NCT01677741||A Study to Determine Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib In Children and Adolescent Subjects [including melanoma patients]||Glaxo-Smith-Kline||Dabrafenib||12 months–17 years||17 Centers USA, Canada, France, Spain, UK|
|NCT01508013||An Appearance-Based Intervention to Reduce Teen Skin Cancer Risk (iSTART)||East Tennessee State University||Behavioral: Appearance-Focused Website Intervention||13–18 years||1 US Center|
|NCT01709435||Cabozantinib in Treating Younger Patients With Recurrent or Refractory Solid Tumors [including melanoma]||National Cancer Institute||Cabozantinib||2–18 years||23 Centers in USA & Canada|
|NCT00931931||HSV1716 in Patients With Non-Central Nervous System (Non-CNS) Solid Tumors [including melanoma]||Nationwide Children’s Hospital||Biological: HSV1716||7–30 years||2 US Centers|
|NCT02147080||A Tailored Internet Intervention to Reduce Skin Cancer Risk Behaviors Among Young Adults (UV4me)||Fox Chase Cancer Center||Behavioral: UV4me/Skin Cancer Foundation website||18–25 years||1 US Center|
- The antibody used in trial NCT00743496 is directed against CD2, which is expressed on the surface of most refractory neuroblastoma, osteosarcoma, Ewing sarcoma, and melanoma tumor cells, which are considered difficult to treat and cure.
- Ipilimumab is FDA approved since March 2011 for late-stage melanoma that has spread or cannot be removed by surgery. In Canada, it is approved for treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease. It is EMA-approved for second line treatment of metastatic melanoma since November 2012.
- Dabrafenib is FDA-approved as a single agent for BRAF V600E mutation-positive advanced melanoma since May 2013.
- Cabozantinib is FDA-approved since November 2012 for medullary thyroid cancer and is currently undergoing clinical trials for multiple other solid cancer types, including melanoma.
- HSV1716 is an oncolytic virus, a mutant herpes simplex virus (HSV) type I, deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells—a phenotype exploited to selectively kill tumor cells. Replication of HSV1716 in human glioblastoma in situ has been demonstrated. Following a single administration of HSV1716 by direct injection into active recurrent tumor or brain adjacent to tumor, some patients have lived longer than might have been expected. This study seeks to evaluate the safety of a single injection of HSV1716 in the treatment of extracranial solid tumors in adolescents and young adults.
Conflicts of Interest
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