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Record Nr. |
UNINA9910631099403321 |
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Titolo |
Pediatric cancer therapeutics development / / editors : Jorge DiMartino, Gregory H. Reaman, Franklin O. Smith |
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Pubbl/distr/stampa |
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Cham, Switzerland : , : Springer, , [2022] |
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©2022 |
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ISBN |
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Descrizione fisica |
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1 online resource (184 pages) |
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Collana |
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Pediatric oncology (Series) |
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Disciplina |
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Soggetti |
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Cancer - Chemotherapy |
Cancer in children - Treatment |
Drug development |
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Lingua di pubblicazione |
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Formato |
Materiale a stampa |
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Livello bibliografico |
Monografia |
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Nota di bibliografia |
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Includes bibliographical references. |
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Nota di contenuto |
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Intro -- Contents -- 1: History of Drug Development for Children with Cancer -- 1.1 Introduction -- 1.2 Initial Progress -- 1.3 Rise of the Cancer Cooperative Groups -- 1.4 Impact of Regulation to Improve Safety and Efficacy Federal Laws Providing a Regulatory Framework for Drug Development in Children -- 1.5 Indications -- 1.6 Summary -- References -- 2: Targeted Small Molecule Drug Discovery -- 2.1 Introduction -- 2.2 Stage Gating -- 2.3 Phenotypic Drug Discovery -- 2.4 Target-Based Drug Discovery: Considerations for Target Selection/Identification -- 2.5 Target-Based Drug Discovery: Identifying Chemical Starting Points -- 2.6 Hit-to-Lead -- 2.7 Lead Optimization -- 2.8 Candidate Nomination -- References -- 3: An FDA Oncology Perspective of Juvenile Toxicity Studies to Support Pediatric Drug Development -- 3.1 Introduction -- 3.2 Should a JAS Be Considered? -- 3.2.1 ICH S11: Nonclinical Safety Testing in Support of Development of Pediatric Medicines -- 3.2.2 ICH S9: Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers -- 3.3 Dinutuximab and Naxitamab -- 3.4 TRK Inhibitors -- 3.5 Conclusion -- References -- 4: Design and Statistical Considerations for Early Phase Clinical Trials in Pediatric Oncology -- 4.1 Introduction -- 4.2 Rule-Based Designs -- 4.2.1 Traditional 3 + 3 Design -- 4.2.2 Accelerated Titration Design -- 4.2.3 Rolling Six Design -- 4.3 |
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Model-Based Designs -- 4.3.1 Continual Reassessment Method (CRM) -- 4.3.2 EWOC and BLRM -- 4.3.3 TITE-CRM and TITE-EWOC -- 4.4 Model-Assisted Designs -- 4.4.1 Modified Toxicity Probability Interval (mTPI) Design -- 4.4.2 Keyboard Design -- 4.4.3 Bayesian Optimal Interval (BOIN) Design -- 4.5 New Designs -- 4.5.1 Modified 4 + 4 Design -- 4.6 Conclusions -- References. |
5: Exploratory Clinical Development: From First in Humans to Phase 3 Ready -- 5.1 Introduction -- 5.2 The Therapeutic Hypothesis -- 5.3 Dose and Schedule Determination -- 5.4 Clinical Proof of Concept (PoC) -- 5.5 Putting It All Together: Combined Phase 1-2 Studies -- 5.6 A Role for Pediatric Cancer in Exploratory Drug Development -- References -- 6: Gene and Cell Therapy: How to Build a BioDrug -- 6.1 Introduction -- 6.2 BioDrug ToolKit: Cells -- 6.2.1 Hematopoietic Stem Cells (HSCs) -- 6.2.2 T Lymphocytes -- 6.2.3 Natural Killer (NK) Cells -- 6.2.4 Macrophages (MΦs) -- 6.2.5 Dendritic Cells (DCs) -- 6.2.6 Mesenchymal Stem Cells (MSCs) -- 6.2.7 Human-Induced Pluripotent Stem Cells (iPSCs) -- 6.2.8 Target Tissues -- 6.3 BioDrug ToolKit: Genetic Material and Gene-Editing Machinery -- 6.4 BioDrug ToolKit: Delivery Systems -- 6.4.1 Viral-Based Delivery Systems -- 6.4.2 Nonviral Delivery Systems -- 6.4.2.1 Chemical Methods of Delivery -- 6.4.2.2 Physical Methods of Delivery -- 6.5 Building a BioDrug -- 6.5.1 Building Gene Therapies: Putting Together Genetic Material, Gene-Editing Machinery, Delivery Systems, and Target Cells -- 6.5.2 Building Gene Therapies: Progress and Challenges -- 6.5.3 Building Cell Therapies: Using the BioDrug ToolKit for Treatment of Malignancy -- 6.5.4 Engineered Cell Therapy: Putting Together Cells, Genetic Material, Gene-Editing Machinery, and Delivery Systems to Target Malignant Cells -- 6.5.4.1 Toxicities of Engineered T cell Therapy -- 6.5.4.2 Building a More Effective T cell BioDrug: Remaining Challenges -- 6.6 Summary -- References -- 7: The Pharma/Biotech Model for Drug Development: Implications for Pediatric Cancer Therapeutics -- 7.1 The Old: Large Pharma -- 7.1.1 Background and History -- 7.1.2 Profile of a Large Pharma: Merck & -- Co. -- 7.2 The New: Biotech. |
7.2.1 Biotech Financing: From Birth to Adulthood -- 7.3 The Drive for Pharmaceutical Innovation -- 7.4 Current Trends in Pharmaceutical R& -- D -- 7.4.1 Open Innovation -- 7.4.2 Small Entrepreneurial Units -- 7.4.3 Virtualization and Outsourcing -- 7.5 Implications for Pediatric Cancer Therapeutics -- References -- 8: Clinical Research Organizations -- 8.1 Introduction -- 8.2 Business Development -- 8.2.1 CRO Team Members -- 8.2.2 Regulatory Affairs -- 8.2.3 Investigational New Drug (IND)/Investigational Device Exemption (IDE) Application -- 8.2.4 FDA Meetings -- 8.2.5 Investigator's Brochure (IB) -- 8.2.6 Annual Reporting -- 8.2.7 Protocol Development and Amendments -- 8.2.8 Feasibility -- 8.2.9 Study Start-Up -- 8.2.10 Site Activation -- 8.2.11 Determining the Impact on Timelines -- 8.3 Project Management -- 8.3.1 Medical Monitoring -- 8.3.2 Clinical Monitoring -- 8.3.3 Safety -- 8.3.4 Clinical Data Management (CDM) -- 8.3.5 Statistics -- 8.3.6 Quality Assurance -- 8.3.7 Risk Management/Risk Mitigation -- 8.3.8 Recruitment and Retention -- 8.4 Conclusion -- References -- 9: Role of Patients and Advocates in Cancer Therapeutics Development -- 9.1 Introduction and Landscape Perspective -- 9.2 A Brief History and the Rise of Advocate Involvement -- 9.3 Defining the Roles of Patients and Advocates -- 9.4 Policy and Regulatory Issues -- 9.4.1 United States -- 9.4.2 Europe -- 9.4.3 Canada -- 9.4.4 Low- and Middle-Income Countries -- 9.5 Support and Learning for Patient Experts -- 9.6 Involving Patient Experts in the Drug Development Life Cycle -- |
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9.6.1 Setting Research Priorities and Catalyzing New Ideas -- 9.6.2 Basic and Translational Research -- 9.6.3 Tumor Tissue for Preclinical Testing -- 9.6.4 Philanthropic Funding of Early Drug Development -- 9.6.5 Clinical Trial Design and Ethics Review. |
9.6.6 Regulatory Approval and Reimbursement -- 9.6.6.1 FDA -- 9.6.6.2 EMA -- 9.6.6.3 HTAs -- 9.7 Collaboration Among Stakeholders to "ACCELERATE" -- 9.7.1 Pediatric Strategy Forums -- 9.8 Challenges and Opportunities -- 9.9 Recommendations for Academic, Industry, and Regulatory Bodies -- 9.10 Summary and What's Next? -- References -- 10: The Role of Regulatory Agencies in Pediatric Cancer Drug Development -- 10.1 Introduction and History of Legislation Affecting Pediatric Drug Development -- 10.1.1 US Regulatory Programs to Expedite Development of Drugs and Biologics -- 10.1.2 European Regulatory Programs to Expedite Development of Drugs and Biologics -- 10.1.3 US Orphan Drug Program -- 10.2 Regulatory Standards for Approval of Drugs and Biologics -- 10.3 Implementation of Pediatric Regulations (Before FDARA) -- 10.3.1 Implementation of Pediatric Regulations in the United States -- 10.3.2 Legislative Requirements for Pediatric Studies -- 10.3.2.1 United States -- 10.3.2.2 European Union -- 10.3.3 Voluntary Incentive Pediatric Development Programs -- 10.3.3.1 United States -- 10.3.3.2 European Union -- 10.4 Impact of US Pediatric Regulations Prior to FDARA on Pediatric Drug Development -- 10.5 Evolving Regulatory Landscape -- 10.5.1 PREA and the RACE for Children Act -- 10.6 Responding to the Changing Cancer Drug Development Paradigm -- 10.6.1 Evolving Cancer Drug Development -- 10.7 International Multi-Stakeholder Collaboration -- 10.8 Prospects for Future Advances -- References -- 11: Ethical Considerations in Pediatric Cancer Therapeutics Development -- 11.1 Introduction -- 11.2 Ethical Principles Defined by the National Commission and Regulatory Framework for Safeguarding Children Involved in Clinical Investigations. |
11.2.1 Additional Safeguards for Children Involved in Clinical Investigations (21 CFR 50, Subpart D) -- 11.3 Interpreting and Applying the Ethical Principles and Regulatory Framework in Pediatric Cancer Therapeutics Development -- 11.3.1 Scientific Necessity and Pediatric Extrapolation -- 11.3.2 Prospect of Direct Benefit in Pediatric Oncology Trials -- 11.3.2.1 Eligibility Criteria: Considerations for the Age of Enrollment -- 11.3.2.2 Early-Phase Pediatric Oncology Trials -- 11.3.2.3 Optimizing Prospect of Direct Benefit: Dose Selection and Study Design in the Era of Molecularly Targeted Products -- 11.3.3 Analysis and Minimization of Risk in Pediatric Oncology Trials -- 11.4 Parental Permission and Child Assent -- 11.5 Conclusions -- References -- 12: Future Directions -- References. |
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