Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Master Protocols for Precision Medicine in Oncology: Overcoming Methodology of Randomized Clinical Trials.

ABSTRACT: Randomized clinical trials are considered the milestones of clinical research in oncology, and guided the development and approval of new compounds so far. In the last few years, however, molecular and genomic profiling led to a change of paradigm in therapeutic algorithms of many cancer types, with the spread of different biomarker-driven therapies (or targeted therapies). This scenario of "personalized medicine" revolutionized therapeutic strategies and the methodology of the supporting clinical research. New clinical trial designs are emerging to answer to the unmet clinical needs related to the development of these targeted therapies, overcoming the "classical" structure of randomized studies. Innovative trial designs able to evaluate more than one treatment in the same group of patients or many groups of patients with the same treatment (or both) are emerging as a possible future standard in clinical trial methodology. These are identified as "master protocols", and include umbrella, basket and platform trials. In this review, we described the main characteristics of these new trial designs, focusing on the opportunities and limitations of their use in the era of personalized medicine.

SUBMITTER: Di Liello R

PROVIDER: S-EPMC8618758 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology.

Project description:BACKGROUND:Clinical trials are an essential part of evidence-based medicine. Hence, to ensure transparency and accountability in these clinical trials, policies for registration have been framed with emphasis on mandatory submission of trial elements, specifically outcome measures. As these efforts evolve further, we sought to evaluate the current status of endpoint reporting in clinical trial registries. METHODS:We reviewed 71 oncology related randomized controlled trials published in three high impact journals. We compared primary (PEP) and non-primary endpoints (NPEP) between the clinical trial protocols of these trials and their corresponding registration in one of the 14 primary global clinical trial registries. A discrepancy was defined as the non-reporting or absence of an endpoint in either the protocol or registry. The primary endpoint was the rate of discrepancy between secondary endpoints in clinical trial protocols and clinical trial registries. RESULTS:Of the 71 clinical trials, a discrepancy in PEP was found in only 4 trials (6%). Secondary endpoint (SEP) differences were found in 45 (63%) trials. Among these 45 trials, 36 (80%) had SEPs that were planned in the protocol but not reported in the registry and 19 (42%) had SEPs with endpoints in the registry that were not found in the protocol. The total number of SEPs that were absent from the corresponding registry and protocol were 84 and 29, respectively. Of these endpoints, 48 (57%) and 9 (31%) were included in the published report of these trials. CONCLUSION:Although recent regulations and enhanced procedures have improved the number and quality of clinical trial registrations, inconsistencies regarding endpoint reporting still exist. Though further guidelines for the registration of clinical trials will help, greater efforts to provide a correct, easily accessible, and complete representation of planned endpoints are needed.

| S-EPMC6292048 | biostudies-other

Precision oncology: A new era of cancer clinical trials.

Project description:Traditionally, site of disease and anatomic staging have been used to define patient populations to be studied in individual cancer clinical trials. In the past decade, however, oncology has become increasingly understood on a cellular and molecular level, with many cancer subtypes being described as a function of biomarkers or tumor genetic mutations. With these changes in the science of oncology have come changes to the way we design and perform clinical trials. Increasingly common are trials tailored to detect enhanced efficacy in a patient subpopulation, e.g. patients with a known biomarker value or whose tumors harbor a specific genetic mutation. Here, we provide an overview of traditional and newer biomarker-based trial designs, and highlight lessons learned through implementation of several ongoing and recently completed trials.

| S-EPMC5023449 | biostudies-other

Precision Oncology: Evolving Clinical Trials across Tumor Types.

Project description:Advances in molecular technologies and targeted therapeutics have accelerated the implementation of precision oncology, resulting in improved clinical outcomes in selected patients. The use of next-generation sequencing and assessments of immune and other biomarkers helps optimize patient treatment selection. In this review, selected precision oncology trials including the IMPACT, SHIVA, IMPACT2, NCI-MPACT, TAPUR, DRUP, and NCI-MATCH studies are summarized, and their challenges and opportunities are discussed. Brief summaries of the new ComboMATCH, MyeloMATCH, and iMATCH studies, which follow the example of NCI-MATCH, are also included. Despite the progress made, precision oncology is inaccessible to many patients with cancer. Some patients' tumors may not respond to these treatments, owing to the complexity of carcinogenesis, the use of ineffective therapies, or unknown mechanisms of tumor resistance to treatment. The implementation of artificial intelligence, machine learning, and bioinformatic analyses of complex multi-omic data may improve the accuracy of tumor characterization, and if used strategically with caution, may accelerate the implementation of precision medicine. Clinical trials in precision oncology continue to evolve, improving outcomes and expediting the identification of curative strategies for patients with cancer. Despite the existing challenges, significant progress has been made in the past twenty years, demonstrating the benefit of precision oncology in many patients with advanced cancer.

| S-EPMC10093499 | biostudies-literature

Precision medicine in pediatric oncology.

Project description:Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.

| S-EPMC6119176 | biostudies-other

Precision medicine clinical trials: defining new treatment strategies.

Project description:ObjectivesTo discuss the role of clinical trials in the changing landscape of cancer care resulting in individualized cancer treatment plans including a discussion of several innovative randomized studies designed to evaluate multiple targeted therapies in molecularly defined subsets of individuals.Data sourcesMedical and nursing literature, research articles, and clinicaltrials.gov.ConclusionRecent advancements in cancer biomarkers and biomedical technology have begun to transform fundamentals of cancer therapeutics and clinical trials through innovative adaptive trial designs. The goal of these studies is to learn not only if a drug is safe and effective but also how it is best delivered and who will derive the most benefit.Implications for nursing practiceImplementation of clinical trials in the cancer biomarker era requires knowledge, skills, and expertise related to the use of biomarkers and molecularly defined processes underlying a malignancy, as well as an understanding of associated ethical, legal, and social issues to provide competent, safe, and effective health care and patient communication.

| S-EPMC4280791 | biostudies-literature

Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples.

Project description:In recent years, cancers once viewed as relatively homogeneous in terms of organ location and treatment strategy are now better understood to be increasingly heterogeneous across biomarker and genetically defined patient subgroups. This has produced a shift toward development of biomarker-targeted agents during a time when funding for cancer research has been limited; as a result, the need for improved operational efficiency in studying many agent-and-target combinations in parallel has emerged. Platform trials, basket trials, and umbrella trials are new approaches to clinical research driven by this need for enhanced efficiency in the modern era of increasingly specific cancer subpopulations and decreased resources to study treatments for individual cancer subtypes in a traditional way. In this review, we provide an overview of these new types of clinical trial designs, including discussions of motivation for their use, recommended terminology, examples, and challenges encountered in their application.

| S-EPMC5834138 | biostudies-other

Precision medicine in pediatric oncology.

Project description:PURPOSE OF REVIEW:The current review describes recent advances and unique challenges in precision medicine for pediatric cancers and highlights clinical trials assessing the clinical impact of targeted therapy matched to molecular alterations identified by tumor profiling. RECENT FINDINGS:Multiple prospective clinical sequencing studies in pediatric oncology have been reported in the last 2 years. These studies demonstrated feasibility of sequencing in the clinic and revealed a rate of actionable variants that justifies the development of precision trials for childhood cancer. A number of precision medicine trials are recently completed, underway or in development and these will be reviewed herein, with a focus on highlighting aspects of precision medicine trial design relevant to pediatric oncology. SUMMARY:The primary results of the first round of pediatric precision oncology clinical trials will provide us with a greater understanding of the clinical impact of linking tumor profiling to selection of targeted therapies. The aggregation of sequencing and clinical data from these trials and the results of biologic investigations linked to these trials will drive further discoveries and broaden opportunities for precision medicine for children with cancer.

| S-EPMC5770114 | biostudies-literature

Precision Medicine in Pediatric Oncology.

Project description:Improvements in outcome have been seen in children and adolescents with cancer. Nevertheless, challenges remain in trying to improve the outcomes for all children diagnosed with cancer, particularly in patients with metastatic disease or with cancers that are resistant or recur after standard treatment. Precision medicine trials using individualized tumor molecular profiling for selection of targeted therapies are ongoing in adult malignancies. Similar approaches are being applied to children and adolescents with cancer. This article describes how precision medicine is being applied to pediatric oncology and the unique challenges being faced with these efforts.

| S-EPMC7819485 | biostudies-literature

Precision Oncology for Cancer Immunotherapies in Early-Phase Clinical Trials.

Project description:The clinical development of cancer drugs is rapidly moving from empirical "one drug fits all" or development-by-tumor-type approaches towards more personalized treatment models. A deeper understanding of cancer and the immune system, novel technologies, and powerful analytics have fueled an increase in precision oncology approaches integrating the molecular profiles of the tumor with the clinical profile of the patient. While this approach has been successful for targeted therapies, the complex mode of action of immunotherapies will likely require integration of clinical profiling with more comprehensive profiling of the tumor, of the tumor microenvironment, and of the immune system of the patient. Integration of precision oncology into clinical research for immunotherapies is viewed as a means to better select patients in the early clinical phase of drug development to (1) maximize the benefit-to-risk ratio for the patient, (2) generate early proof of concept and proof of relevance for the investigational drug, and (3) inform on how to best combine or sequence the therapeutic with other drugs. Here we discuss the upsides and challenges of incorporating precision immuno-oncology into early-phase clinical trials.

| S-EPMC6875515 | biostudies-literature

Next-generation ctDNA-driven clinical trials in precision immuno-oncology.

Project description: Not available

| S-EPMC9853228 | biostudies-literature