Practical Considerations and Recommendations for Master Protocol Framework: Basket, Umbrella and Platform Trials

Lu, Chengxing; Li, Xiaoyun Nicole; Broglio, Kristine; Bycott, Paul; Jiang, Qi; Li, Xiaoming; McGlothlin, Anna; Tian, Hong; Ye, Jingjing

doi:10.1007/s43441-021-00315-7

Cited by 35 publications

(36 citation statements)

References 57 publications

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“…Platform trials use a single master protocol to simultaneously evaluate multiple experimental treatments. 54 , 55 The master protocol defines the inclusion and exclusion criteria. On inclusion, a patient is randomized to the control arm or one of the experimental treatment arms.…”

Section: Clinical Trials In Vwmmentioning

confidence: 99%

Therapy Trial Design in Vanishing White Matter

et al. 2022

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Vanishing white matter (VWM) is a leukodystrophy caused by recessive variants in the genes EIF2B1-EIF2B5. It is characterized by chronic neurologic deterioration with superimposed stress-provoked episodes of rapid decline. Disease onset spans from the antenatal period through senescence. Age at onset predicts disease evolution for patients with early onset, whereas disease evolution is unpredictable for later onset; patients with infantile and early childhood onset consistently have severe disease with rapid neurologic decline and often early death, whereas patients with later onset have highly variable disease. VWM is rare, but likely underdiagnosed, particularly in adults. Apart from measures to prevent stressors that could provoke acute deteriorations, only symptomatic care is currently offered. With increased insight into VWM disease mechanisms, opportunities for treatment have emerged. EIF2B1-EIF2B5 encode the 5-subunit eukaryotic initiation factor 2B complex, which is essential for translation of mRNAs into proteins and is a principal regulator of the integrated stress response (ISR). ISR deregulation is central to VWM pathology. Targeting components of the ISR has proven beneficial in mutant VWM mouse models, and several drugs are now in clinical development. However, clinical trials in VWM pose considerable challenges: low numbers of known patients with VWM, unpredictable disease course for patients with onset after early childhood, absence of intermediate biomarkers, and novel first-in-human molecular targets. Given these challenges and considering the critical need to offer therapies, we have formulated recommendations for enhanced diagnosis, drug trial setup, and patient selection, based on our expert evaluation of molecular, laboratory, and clinical data.

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Section: Clinical Trials In Vwmmentioning

confidence: 99%

Therapy Trial Design in Vanishing White Matter

et al. 2022

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“…These studies evaluate targeted therapy for multiple diseases that share common molecular alterations or risk factors. Basket trials assess a single investigational drug or drug combination in different oncological populations that differ in several factors: disease stage, histology, number of prior therapies, genetic or other biomarkers, or demographic characteristics [ 57 , 58 ].…”

Section: Targeted Therapy For Cancermentioning

confidence: 99%

“…Furthermore, each subclass of genetic therapy has inherent limitations. For example, oncolytic viruses can affect only viral antigens, limiting the effectiveness of OV therapy; the reaction and the immune response have significant individual variability, and a relevant problem is the rapid viral elimination of OVs from the organism [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. In addition, CAR-T therapy requires a very complex lymphodepletion process, implemented with chemotherapy before infusion; the consequent risk of serious adverse events such as cytokine release syndrome calls for immediate management and advanced clinical skills [ 72 ].…”

Section: Innovative Treatments: Advantages and Limitationsmentioning

confidence: 99%

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice

Orzetti

Tommasi

Bertola

et al. 2022

IJMS

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The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes—mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential toxicities and adverse drug reactions. Although clinicians often consider pharmacovigilance a non-priority area, it highlights the risk/benefit ratio, an essential factor, especially for these advanced therapies, which represent the most innovative and promising horizon in oncology.

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“…We have focussed on the parallel-group multi-arm trial design, but various perspectives on the need for multiplicity adjustments in more complex designs such as basket, umbrella and platform trials are also being debated [ 14 , [24] , [25] , [26] , [27] , [28] ]. Such new and adaptive designs are increasingly important, especially in the case of COVID-19 where adaptive, cost-effective and rapid trials are critical [ 24 ].…”

mentioning

confidence: 99%