Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. Layout table for location contacts Contact: Mirati Therapeutics Study Locator Services miratistudylocator emergingmed. More Information. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Phase 3. Study Type :. Interventional Clinical Trial. Estimated Enrollment :. Actual Study Start Date :.
Estimated Primary Completion Date :. Estimated Study Completion Date :. During informed consent, the doctor will:. Describe all of the treatment options so that the person understands how the new treatment differs from the standard treatment.
List all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Explain what will be required of each person in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.
You and the research team will carefully review these criteria together. People who participate in a clinical trial may stop participating at any time for personal or medical reasons.
This may include that the new treatment is not working or there are serious side effects. Clinical trials are also closely monitored by experts who watch for any problems with each study.
Research through clinical trials is ongoing for all types of cancer. Net offers a lot of information about cancer clinical trials in other areas of the website, including a complete section on clinical trials and places to search for clinical trials for a specific type of cancer.
In addition, this website offers free access to a video-based educational program about cancer clinical trials, located outside of this guide. The next section in this guide is Latest Research. It explains areas of scientific research for SCLC. Use the menu to choose a different section to read in this guide. What are clinical trials?
Deciding to join a clinical trial People decide to participate in clinical trials for many reasons. Patient safety and informed consent To join a clinical trial, people must participate in a process known as informed consent.
During informed consent, the doctor will: Describe all of the treatment options so that the person understands how the new treatment differs from the standard treatment. Describe the purposes of the clinical trial and what researchers are trying to learn. Finding a clinical trial Research through clinical trials is ongoing for all types of cancer. Memory loss, intellectual deficit, dementia and ataxia have been reported, often in patients with cerebral atrophy and white matter changes on brain imaging.
It is recognized that, in addition to PCI, a number of factors can affect neurocognition, including underlying comorbidities caused by smoking, paraneoplastic syndromes, underlying anxiety and depression, chemotherapy, and SCLC itself. This is supported by studies demonstrating impairment in neuropsychological tests in patients with SCLC, even before PCI is given , Minimizing neurotoxicity is an important goal of ongoing clinical trials, including those evaluating the benefit of hippocampus-sparing PCI and comparing PCI to MRI surveillance Progress on several fronts is defining new avenues of investigation and providing renewed hope for patients with this recalcitrant cancer.
Many new insights regarding SCLC biology have stemmed from the development and analysis of representative genetically engineered mouse models of SCLC and these insights have been complemented and reinforced by parallel analyses of SCLC cell lines, patient-derived in vivo models and primary human tumours Analyses of mechanisms of in vivo-acquired therapeutic resistance in SCLC through both transcriptomic 77 and proteomic 46 approaches have revealed new potential tumour-specific vulnerabilities.
The new understanding of key transcriptional drivers of SCLC phenotypes, defining subtypes of disease with distinct dependencies, might help to focus therapeutic clinical research on patient populations that are most likely to respond to particular targeted agents Technological improvements in imaging and in the advanced delivery of radiotherapy have increased the survival rates of patients with localized disease, while reducing the short-term and long-term adverse effects The introduction of immunotherapy as part of standard treatment for many patients with metastatic SCLC has finally led to improvements in overall survival for this cohort of patients with a particularly poor prognosis , These and other advances underscore tangible progress in the management of SCLC and have defined a number of novel therapeutically tractable targets for this disease FIG.
Many key targets highlighted are being actively pursued in completed and upcoming clinical trials. Despite these highlights, SCLC remains a largely lethal disease. Several gaps exist in our understanding of the disease, which contribute to the modest effect that current treatments have had on patient survival. Notably, the societal impact of SCLC could be obviated with effective prevention, especially as the aetiologic agent in oncogenesis is exceptionally clear.
SCLC is among the diseases most strongly associated with tobacco carcinogen exposure The importance of global and multifaceted public health advocacy and governmental regulatory approaches to reduce the initiation of smoking and increase smoking cessation cannot be overemphasized.
The effective screening for incipient SCLC is a major and entirely unmet need. Highly sensitive, blood-based detection using mutational, proteomic or multiparameter approaches is an area of active investigation. Preclinical studies suggest the detection of neuroendocrine markers through mass spectrometry as one potential approach Most patients with SCLC die of metastatic disease. As noted, annual CT screening in a high-risk population fails to detect early-stage SCLC — with or without screening, an identical majority of patients have stage IV disease at diagnosis This observation might imply a biological difference between limited-stage SCLCs, which commonly present with a large primary mass and bulky adenopathy, and extensive-stage SCLCs, which often present with widespread metastases at diagnosis.
Studies have uncovered remarkable intertumoural and intratumoural heterogeneity in SCLC. We are only beginning to dissect how this heterogeneity influences the biology of disease. We are only beginning to understand the extent to which subtype assignments are mutable and whether tumour evolution between subtypes reflects lineage plasticity or differential selection among pre-existing subclones Multiple recurrent mutations affecting epigenetic regulatory pathways in SCLC have been defined 24 , 40 , 41 , 77 ; how these epigenetic pathways could either determine or drive the transition between transcriptional states is unknown.
Despite hypothesized subtype-specific vulnerabilities , the extent to which different predominant subtypes in fact influence clinical prognosis, therapeutic responsiveness and patterns of disease progression has not been defined.
Intratumoural hetero geneity, including a mix of interacting neuroendocrine and non-neuroendocrine subpopulations, has been implicated in metastatic potential in mouse models 39 , but has been less extensively characterized in human tumours. Emerging technical advances in single-cell profiling technologies, including single-cell transcriptional profiling, proteomic profiling and spatial multicolour imaging, are ideally suited to begin to study some of these issues.
The advent of chemo-immunotherapy as a new standard of care for the first-line treatment of metastatic disease , is both a remarkable hallmark of progress and a disappointment. The overall improvement in survival in patients with SCLC from the addition of immune checkpoint blockade is modest relative to that seen in many other solid tumours, despite a highly mutated genome in SCLC tumours.
An intensive focus of clinical research is now on the exploration of complementary pathways to immune activation, including the blockade of alternative immune checkpoints, the use of bispecific T cell engagers or natural killer cell activators, and assessing DNA damage response inhibitors or epigenetically targeted agents as strategies to induce immune-responsiveness in SCLC Similar challenges to improving survival also apply to early-stage and locally advanced SCLC. Building on the successes in treating metastatic disease, multiple trials are in development or in progress to assess the role of PD1—PDL1 checkpoint blockade in patients treated with CRT.
It would be of substantial interest to know if sensitive methods for the detection of circulating tumour DNA in blood and, possibly, in cerebrospinal fluid could be used to identify those patients who might benefit from additional treatment, such as PCI or additional systemic therapies, versus those who are likely to be cured by thoracic CRT alone.
The advances of the past decade in defining the genetics and biological pathways driving SCLC have identified multiple novel therapeutic strategies. The pace of laboratory research in SCLC has dramatically accelerated, facilitated in large part by an expansion of the number and diversity of representative preclinical models. Several novel therapeutic targets are being actively pursued in clinical research today.
We believe that continuing to use emerging insights gained from laboratory studies to inform and focus clinical trials is likely to yield clinically meaningful progress for patients with SCLC in the decade ahead. The authors thank Nina Beaty for her contribution in Box 1. He serves on the scientific advisory boards of Bridge Medicines and Harpoon Therapeutics. National Center for Biotechnology Information , U.
Nat Rev Dis Primers. Author manuscript; available in PMC Jun 4. Charles M. Find articles by Charles M. Find articles by Elisabeth Brambilla. Find articles by Corinne Faivre-Finn. Find articles by Julien Sage. Author information Copyright and License information Disclaimer.
Author contributions Introduction C. Copyright notice. The publisher's final edited version of this article is available at Nat Rev Dis Primers. See other articles in PMC that cite the published article. Open in a separate window. Common sites of metastasis in SCLC. Epidemiology Incidence and prevalence Lung cancer is the leading cause of cancer mortality worldwide, with an estimated 2.
Risk factors SCLC is among the cancers with the strongest epidemiological link to tobacco, and its prevalence tends to mirror the prevalence of smoking, with a lag time of about 30 years SCLC incidence and survival statistics. SCLC, small-cell lung cancer. Molecular pathways affected in SCLC Both RB and p53 play key roles in regulating cell cycle progression: RB is a major inhibitor of S phase entry, whereas p53 is integral to multiple cell cycle checkpoints, triggering cell cycle arrest or inducing apoptosis in response to various cellular stresses, for example, aberrant replication.
Drivers and trajectories of metastasis SCLC metastases are rarely resected in patients but insights into the biology of SCLC metastasis have come from both the study of CTCs and the development of mouse models. Immune evasion SCLC cells have a high tumour mutation burden and, on this basis, are predicted to induce strong T cell responses.
An emerging molecular classification While the SCLC tumour mutational landscape does not seem to define subtypes, the expression of specific transcription factors provides a first framework to differentiate biologically distinct SCLC subtypes.
Major genetic alterations and molecular subtypes of SCLC. Diagnosis, screening and prevention SCLC is a high-grade malignant epithelial tumour. Signs and symptoms Distinct clinical characteristics of SCLC include the predominantly central location of the primary tumour in the major airways and the often extensive extrapulmonary metastatic spread at presentation.
Diagnostic work-up Given the aggressive nature of SCLC, diagnostic and staging work-up should be performed as quickly as possible after presentation. Staging The tumour—node—metastasis TNM classification is preferred to the previous staging system of the Veterans Administration Lung Study Group VALSG , which separates limited-stage disease tumour confined to one hemi-thorax and one radiation port; no malignant pleural or pericardial effusion from extensive-stage disease disease not meeting criteria for limited stage Histopathology of SCLC tumours.
Differential diagnoses. Screening and prevention Screening by low-dose CT in patients at risk for lung cancer smokers and ex-smokers has detected newly diagnosed SCLC cases. Approaches to SCLC treatment by stage. Metastatic disease For over three decades, the first-line chemotherapy for newly diagnosed metastatic SCLC has consisted of a platinum agent cisplatin or carboplatin together with etoposide 1. Quality of life Personalized treatment is at the heart of modern oncology and should consider the risk to benefit ratio of therapy for each individual patient.
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