scholarly journals Precision Medicine for Molecularly Targeted Agents and Immunotherapies in Early-Phase Clinical Trials

2015 ◽  
Vol Suppl. 1 ◽  
pp. 1-11 ◽  
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Early Phase ◽  
Targeted Agents ◽  
Molecularly Targeted Agents ◽  
Early Phase Clinical Trials

scholarly journals Bayesian adaptive design of early-phase clinical trials for precision medicine based on cancer biomarkers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shinjo Yada
Keyword(s):  
Neural Network ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Early Phase ◽  
Patient Specific ◽  
Specific Gene ◽  
Cancer Type ◽  
Background Characteristics ◽  
Number Of Patients ◽  
Early Phase Clinical Trials

Abstract Cancer tissue samples obtained via biopsy or surgery were examined for specific gene mutations by genetic testing to inform treatment. Precision medicine, which considers not only the cancer type and location, but also the genetic information, environment, and lifestyle of each patient, can be applied for disease prevention and treatment in individual patients. The number of patient-specific characteristics, including biomarkers, has been increasing with time; these characteristics are highly correlated with outcomes. The number of patients at the beginning of early-phase clinical trials is often limited. Moreover, it is challenging to estimate parameters of models that include baseline characteristics as covariates such as biomarkers. To overcome these issues and promote personalized medicine, we propose a dose-finding method that considers patient background characteristics, including biomarkers, using a model for phase I/II oncology trials. We built a Bayesian neural network with input variables of dose, biomarkers, and interactions between dose and biomarkers and output variables of efficacy outcomes for each patient. We trained the neural network to select the optimal dose based on all background characteristics of a patient. Simulation analysis showed that the probability of selecting the desirable dose was higher using the proposed method than that using the naïve method.

Abstract A185: Combining unbiased network analysis and cancer genomics to guide precision medicine-oriented early-phase clinical trials

2018 ◽  
Author(s):  
Pedro Torres-Ayuso ◽  
Sudhakar Sahoo ◽  
Christopher Chester ◽  
Cassandra Hodgkinson ◽  
Melanie Galvin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Network Analysis ◽  
Precision Medicine ◽  
Early Phase ◽  
Cancer Genomics ◽  
Early Phase Clinical Trials

scholarly journals Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in precision-medicine oriented early phase clinical trials

2018 ◽  
Author(s):  
◽  
Sudhakar Sahoo ◽  
Melanie Galvin ◽  
Hui Sun Leong ◽  
Kristopher K Frese ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
High Throughput ◽  
Early Phase ◽  
Drug Efficacy ◽  
Early Phase Clinical Trials ◽  
Generation Sequencing

AbstractPrecision medicine aims to tailor cancer therapies to target specific tumorpromoting aberrations. For tumors that lack actionable drivers, extensive molecular characterization and pre-clinical drug efficacy studies will be required to match patients with the appropriate targeted therapy. A cell line maintained at low passage and a patient-derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patient’s DNA; however, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and RICTOR genes, respectively. Consistent with amplification of these genes, pathway analysis revealed activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis complements next-generation sequencing approaches for detection of actionable alterations and will aid in patient stratification into early-phase clinical trials.

Precision medicine in recurrent glioblastoma: A feasibility trial conducted by the Ivy Foundation Early Phase Clinical Trials Consortium.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2031-2031 ◽  
Author(s):  
Michael Prados ◽  
John G. Kuhn ◽  
Howard Colman ◽  
Timothy Francis Cloughesy ◽  
Susan Marina Chang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Early Phase ◽  
Recurrent Glioblastoma ◽  
Feasibility Trial ◽  
Early Phase Clinical Trials

Tissue Collection for Correlative Studies in Childhood Cancer Clinical Trials: Ethical Considerations and Special Imperatives

2004 ◽  
Vol 22 (23) ◽  
pp. 4846-4850 ◽  
Author(s):  
Barry D. Anderson ◽  
Peter C. Adamson ◽  
Susan L. Weiner ◽  
Mary S. McCabe ◽  
Malcolm A. Smith
Keyword(s):  
Clinical Trials ◽  
Childhood Cancer ◽  
Early Phase ◽  
Targeted Agents ◽  
Children With Cancer ◽  
Pediatric Study ◽  
Molecularly Targeted Agents ◽  
Correlative Studies ◽  
Tissue Specimens ◽  
Research Studies

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.

Ocular Toxicity of Targeted Therapies

2012 ◽  
Vol 30 (26) ◽  
pp. 3277-3286 ◽  
Author(s):  
Daniel J. Renouf ◽  
Juan P. Velazquez-Martin ◽  
Rand Simpson ◽  
Lillian L. Siu ◽  
Philippe L. Bedard
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Cytotoxic Chemotherapy ◽  
Ocular Toxicity ◽  
Targeted Agents ◽  
Ocular Tissues ◽  
Molecularly Targeted Agents ◽  
Oncology Practice ◽  
Early Phase Clinical Trials ◽  
Management Recommendations

Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ophthalmologist. Ongoing collaboration between oncologists and ocular disease specialists is critical as the use of molecularly targeted agents continues to expand and novel targeted drug combinations are developed.

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