scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

scholarly journals Is there a role for adjuvant therapy after surgery in “high risk for recurrence” kidney cancer? An update on current concepts

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
T. Sharma ◽  
C. Tajzler ◽  
A. Kapoor
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Patient Population ◽  
Treatment Options ◽  
Significant Proportion ◽  
High Risk Patient ◽  
Disease Free Survival ◽  
Cochrane Reviews

BackgroundAlthough surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed.MethodsA literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/ databases included the keywords “adjuvant therapy,” “renal cell carcinoma,” and “targeted therapy or/and immunotherapy.”ConclusionsData from the s-trac study indicated that, in the “highest risk for recurrence” patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the “intermediate- to high-risk” patient population. The ariser (adjuvant girentuximab) and protect (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the “high risk of recurrence” category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials.

scholarly journals The path to innovative drug development of cancer vaccine: From discovery of tumor antigens to clinical trials

2014 ◽  
Vol 37 (2) ◽  
pp. 90-95 ◽  
Author(s):  
Toshihiko TORIGOE ◽  
Yoshihiko HIROHASHI ◽  
Tomohide TSUKAHARA ◽  
Takayuki KANASEKI ◽  
Vitaly KOCHIN ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Cancer Vaccine ◽  
Tumor Antigens ◽  
Innovative Drug

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

Reversal of Renal Insufficiency in an Aging Cat: A 5-year Multi-Crossover Case Study

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Robert Dennis ◽  
John Dennis
Keyword(s):  
Palliative Care ◽  
Renal Insufficiency ◽  
Treatment Options ◽  
Low Frequency ◽  
Standard Of Care ◽  
Omega 3 ◽  
Current Standard ◽  
Invasive Treatment ◽  
Non Invasive ◽  
Electro Magnetic

Renal failure is a leading cause of suffering and death in domestic cats, with approximately 1 in 3 cats affected.  Current standard-of-care treatment usually involves palliative care, diets restricted in protein and phosphorus, plenty of fluids, and sometimes vitamin D and Omega-3.  But even with early detection, which is difficult, treatment options are limited and often are not very effective.  Dietary restrictions and palliative care are often the best that can be offered, but the creatinine levels tend to inexorably creep upward toward eventual kidney failure and death.  We report the effectiveness of the use of a low-frequency, low-intensity, non-invasive treatment using Pulsed Electro-Magnetic Fields, specifically tuned to inductively generate micro-electric currents in deep tissues (ICES®-PEMF).  This report chronicles the return to normal and then reversion to renal insufficiency in a single cat, when ICES®-PEMF was applied, then withheld, then applied again, over three cycles of application and non-application, over a 5-year period. A return to normal creatinine levels, with a subsequent return to renal insufficiency as indicated by loss of control of creatinine, correlated precisely with the application and non-application of ICES®-PEMF.  The pattern observed during each cycle was as follows:  when applied 2 to 3 times weekly for 20-60 minutes each treatment, creatinine levels declined to normal range within 2-3 months.  During periods when treatment was discontinued, creatinine levels began to climb to high levels again.  We suggest the further study and potential use of ICES®-PEMF as an effective, inexpensive, safe, non-invasive treatment for feline kidney disease.

scholarly journals Towards Personalization in the Curative Treatment of Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Astrid E. Slagter ◽  
Marieke A. Vollebergh ◽  
Edwin P. M. Jansen ◽  
Johanna W. van Sandick ◽  
Annemieke Cats ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Molecular Characteristics ◽  
Perioperative Chemotherapy ◽  
Current Standard ◽  
Common Cancer ◽  
Resectable Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide and has a high mortality rate. In the last decades, treatment strategy has shifted from an exclusive surgical approach to a multidisciplinary strategy. Treatment options for patients with resectable gastric cancer as recommended by different worldwide guidelines, include perioperative chemotherapy, pre- or postoperative chemoradiotherapy and postoperative chemotherapy. Although gastric cancer is a heterogeneous disease with respect to patient-, tumor-, and molecular characteristics, the current standard of care is still according to a one-size-fits-all approach. In this review, we discuss the background of the different treatment strategies in resectable gastric cancer including the current standard, the specific role of radiotherapy, and describe the current areas of research and potential strategies for personalization of therapy.

scholarly journals CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence

2019 ◽  
Vol 25 (2) ◽  
pp. 95-105
Author(s):  
Agata Blasiak ◽  
Jeffrey Khong ◽  
Theodore Kee
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Standard Of Care ◽  
Small Data ◽  
Current Standard ◽  
Dose Selection ◽  
Support Tool ◽  
Combination Treatments ◽  
Multiple Challenges ◽  
Over Time

The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials’ results provide the basis for guidance and support for official protocols that clinicians use to base their decisions upon. However, individuals rarely demonstrate the reported response from relevant clinical trials, often the average from a group representing a population or subpopulation. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual’s response to the treatment varies over time with the changes in his or her condition, whether via the indication or physiology. In practice, the drug and the dose selection depend greatly on the medical protocol of the healthcare provider and the medical team’s experience. As such, the results are inherently varied and often suboptimal. Big data approaches have emerged as an excellent decision-making support tool, but their application is limited by multiple challenges, the main one being the availability of sufficiently big datasets with good quality, representative information. An alternative approach—phenotypic personalized medicine (PPM)—finds an appropriate drug combination (quadratic phenotypic optimization platform [QPOP]) and an appropriate dosing strategy over time (CURATE.AI) based on small data collected exclusively from the treated individual. PPM-based approaches have demonstrated superior results over the current standard of care. The side effects are limited while the desired output is maximized, which directly translates into improving the length and quality of individuals’ lives.

scholarly journals Systemic treatment options for advanced biliary tract carcinoma

2020 ◽  
Vol 55 (10) ◽  
pp. 944-957
Author(s):  
Changqing Xie ◽  
Nicole A. McGrath ◽  
Cecilia Monge Bonilla ◽  
Jianyang Fu
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Biliary Tract ◽  
Treatment Options ◽  
Single Agent ◽  
Current Status ◽  
Dna Mismatch ◽  
First Line Therapy ◽  
Molecular Landscape ◽  
Line Setting

Abstract Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC.

Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?

2018 ◽  
pp. 280-291 ◽  
Author(s):  
Elizabeth Cartwright ◽  
Florence K. Keane ◽  
Peter C. Enzinger ◽  
Theodore Hong ◽  
Ian Chau
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Global Consensus ◽  
Esophagogastric Cancer ◽  
Genetic Features ◽  
Related Mortality ◽  
Optimal Treatment Strategy

Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.

scholarly journals The interaction between equipoise and logistics in clinical trials: A case study

2017 ◽  
Vol 14 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Meredith G Warshaw ◽  
Vincent J Carey ◽  
Elizabeth J McFarland ◽  
Liza Dawson ◽  
Elaine Abrams ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Standard Of Care ◽  
Design Stage ◽  
Ethical Review ◽  
Clinical Equipoise ◽  
Expert Clinician ◽  
Barriers To Enrollment

Introduction: Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Background: Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician’s sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers’ willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. Case Study: A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. Discussion: When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

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