Breaking News
December 14, 2018 - Scientists perform lung lavage as new approach for tuberculosis diagnosis in rhinoceros
December 14, 2018 - Recent winners of the Nobel Medicine Prize
December 14, 2018 - KHN’s ‘What the Health?’ Insurance enrollment is lagging — and there are lots of reasons why
December 14, 2018 - Study assesses safety and efficacy of new treatment for pancreatic cancer
December 14, 2018 - Study finds drug targets for Ebola, Dengue, and Zika viruses
December 14, 2018 - Study highlights need for personalized approach to treat ICU acquired delirium
December 14, 2018 - Massage helps relieve pain, improve mobility in patients with knee osteoarthritis
December 14, 2018 - Average outpatient visit in the U.S. costs nearly $500, shows new study
December 14, 2018 - Reference Infliximab, Biosimilar Equivalent for Crohn’s Disease
December 14, 2018 - New contact lens to treat eye injuries
December 14, 2018 - Acne could have a genetic basis find researchers promising new cure
December 14, 2018 - Higher physical activity associated with improved mood
December 14, 2018 - New UGA study points to optimal hypertension treatment for stroke patients
December 14, 2018 - Study highlights factors that can reduce food cravings
December 14, 2018 - Researchers discover Ebola-fighting protein in human cells
December 14, 2018 - Fentanyl surpasses heroin in cause of U.S. drug overdose deaths
December 14, 2018 - When Heart Attack Strikes, Women Often Hesitate to Call for Help
December 14, 2018 - A warning about costume contacts
December 14, 2018 - Study examines link between peripheral artery disease and heart attack
December 14, 2018 - Researchers develop biotechnological tool to produce antifungal proteins in plants
December 14, 2018 - 3D-printed adaptive aids can benefit patients with arthritis
December 14, 2018 - Chronic bullying during adolescence impacts mental health
December 14, 2018 - Integral Molecular and Merus collaborate to develop bispecific antibody therapeutics
December 13, 2018 - Importance of cell cycle and cellular senescence in the placenta discovered
December 13, 2018 - Gold “nanoprisms” open new window into vessels and single cells
December 13, 2018 - Research findings could lead to new targets for cancer-fighting therapeutics
December 13, 2018 - Butantan Institute signs collaboration agreement with MSD to develop dengue vaccines
December 13, 2018 - Study explores how patients want to discuss symptoms with doctors
December 13, 2018 - RUDN medics first to gather scattered data on hepatitis morbidity in Somalia
December 13, 2018 - Age and gender disparities found in use of bed nets to prevent malaria in sub-Saharan Africa
December 13, 2018 - Caffeine therapy benefits developing brains of premature babies
December 13, 2018 - New review focuses on electrospinning techniques used in musculoskeletal tissue engineering
December 13, 2018 - A new division focused on human immune system
December 13, 2018 - Zogenix Announces Positive Phase 3 Trial Results on the Efficacy and Safety of Fintepla (ZX008) in Dravet Syndrome
December 13, 2018 - BCR ABL Genetic Test: MedlinePlus Lab Test Information
December 13, 2018 - Caffeinated beverages during pregnancy linked to lower birth weight babies
December 13, 2018 - Stanford Medicine Health Trends Report examines opportunity to democratize health care
December 13, 2018 - Obsessive-compulsive disorder may protect individuals from obesity
December 13, 2018 - Scientists investigate how a painful event is processed in the brain
December 13, 2018 - Genetic study reveals new insights into underlying causes of moderate-to-severe asthma
December 13, 2018 - Study uncovers new genetic clues to frontotemporal dementia
December 13, 2018 - Vitamin C supplementation for pregnant smokers may reduce harm to infants’ lungs
December 13, 2018 - New study reveals yin-yang personality of dopamine
December 13, 2018 - Research identifies nerve-signaling pathway behind sustained pain after injury
December 13, 2018 - Children with high levels of callous traits show widespread differences in brain structure
December 13, 2018 - Long-term Benefit of Steroid Injections for Knee Osteoarthritis Challenged
December 13, 2018 - Adding new channels to the brain remote control
December 13, 2018 - In the Spotlight: A different side of neuroscience
December 13, 2018 - Medical Marvels: Using immunotherapy for melanoma that spread to the brain
December 13, 2018 - Puzzles do not keep dementia away finds study
December 13, 2018 - New mouse model shows potential for rapid identification of promising muscular dystrophy therapies
December 13, 2018 - Study reveals urban and rural differences in prenatal exposure to essential and toxic elements
December 13, 2018 - New collaborative partnership in quest of novel antibiotics
December 13, 2018 - Single tau molecule holds clues to help diagnose neurodegeneration in its earliest stages
December 13, 2018 - AHA Scientific Statement: Low Risk of Side Effects for Statins
December 13, 2018 - What Is Acute Flaccid Myelitis?
December 13, 2018 - How bereaved people control their thoughts without knowing it
December 13, 2018 - Health care democratization underway, according to 2nd annual Stanford Medicine Health Trends Report | News Center
December 13, 2018 - Going Beyond a Single Color
December 13, 2018 - London-based startup launches ‘thedrug.store’ aiming to clean up CBD industry
December 13, 2018 - Loss of tight junction barrier protein results in gastric cancer development
December 13, 2018 - Novel way to efficiently deliver anti-parasitic medicines
December 13, 2018 - RKI publishes new data on disease prevention and utilization of medical services
December 13, 2018 - High-tech, flexible patches sewn into clothes could help to stay warm
December 13, 2018 - The CCA releases three reports on requests for medical assistance in dying
December 13, 2018 - Restoring Hair Growth on Scarred Skin? Mouse Study Could Show the Way
December 13, 2018 - Probiotic use may reduce antibiotic prescriptions, researchers say
December 13, 2018 - Drug repositioning strategy identifies potential new treatments for epilepsy
December 13, 2018 - Chronic rhinitis associated with hospital readmissions for asthma and COPD patients
December 13, 2018 - Food poisoning discovery could save lives
December 13, 2018 - Cloned antibodies show potential to treat, diagnose life-threatening fungal infections
December 13, 2018 - Exercise may reduce colorectal cancer risk after weight loss
December 13, 2018 - Russian scientists create hardware-information system for brain disorders treatment
December 13, 2018 - Moderate alcohol consumption linked with lower risk of hospitalization
December 13, 2018 - Nurturing Healthy Neighborhoods | NIH News in Health
December 13, 2018 - Rise in meth and opioid use during pregnancy
December 13, 2018 - Researchers gain new insights into pediatric tumors
December 13, 2018 - FSU study finds racial disparity among adolescents receiving flu vaccine
December 13, 2018 - Study investigates attitudes toward implementation of ‘sex as a biological variable’ policy
December 13, 2018 - Drug cocktail induces cancer cell death by switching off energy supply
Experts report new guidelines for clinical trial design in patients with brain metastases

Experts report new guidelines for clinical trial design in patients with brain metastases

image_pdfDownload PDFimage_print

Clinical trials of new anti-cancer therapies have often excluded patients whose disease has spread to the brain or central nervous system (CNS) or, if such patients were allowed on trial, trials have often failed to clearly capture information on the drug’s effect in the brain. Today new guidelines from an international, multidisciplinary group published in the journal Lancet Oncology describe how to most appropriately address cancer patients with CNS involvement within clinical trials of anti-cancer drugs.

“Two major situations needed to be optimized. Firstly, as we’ve actually started to see some new anti-cancer drugs working well inside the brain, we needed to find a way to appropriately include these patients in clinical trials so that the trials could accurately capture that benefit. And secondly, for drugs that would be unlikely to work in the brain, we needed to limit risks to patients and to the drug development process,” says D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, director of Thoracic Oncology at the CU School of Medicine and the lead author of the trial design guidelines.

The expert working group which developed these guidelines, called the Response Assessment in Neuro-Oncology – Brain Metastases (RANO-BM) group, also includes researchers from Dana-Farber Cancer Institute, City of Hope National Medical Center, Cleveland Clinic, University of Heidelberg in Germany, University of California at San Francisco, Queen’s University in Canada, University of Groningen and Erasmus University Medical Center in the Netherlands, University of Turin in Italy, Massachusetts General Hospital, University of Virginia, M.D. Anderson Cancer Center, and Columbia University Medical Center.

“Historically, patients with brain metastases were excluded from the majority of systemic therapy trials for a number of reasons, including the misperception that they are poor clinical trial candidates. However, many studies show that select patients with brain metastases can safely enroll on clinical trials, without harm to the patient or to the drug development process,” says Eudocia Lee, MD, MPH, assistant professor of Neurology at the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and co-lead author of the guidelines.

The guidelines adopt a pragmatic approach, suggesting one of three specific strategies based on initial understanding of a drug’s possible activity in the brain. First, when a new drug is considered very unlikely to have activity in the brain, patients with stable CNS disease should be permitted, while those with active CNS disease should be excluded from trials of systemic therapy. Second, if there is some initial evidence that a drug may have activity in the brain, the guidelines propose including patients with both stable and active CNS disease in a way that will capture data defining a drug’s activity in the brain separate from its activity in the rest of the body. Third, when it’s unclear whether a drug may have activity in the brain (as is often the case at the start of any new drug development process), the guidelines suggest including a dedicated cohort of patients with brain metastases very early in drug development to generate the data that would allow trial designers to adopt one of the other two trial designs.

The new guidelines reflect the contributors’ firsthand experiences developing new targeted therapies across cancer subtypes.

“For some subtypes of breast cancer, including HER2-positive or triple-negative, the incidence of brain metastases in patients who have recurrent/metastatic disease approaches 50 percent. Making progress against these subtypes of breast cancer very much depends on developing new and better treatments for brain metastases. Our hope is that by providing investigators with a roadmap for clinical trial design, we can encourage more studies focused on this challenging clinical problem. These new guidelines aim to fundamentally change drug development for advanced cancers,” says Nancy U. Lin, MD, clinical director of the Breast Oncology Center at the Susan F. Smith Center for Women’s Cancers at Dana Farber Cancer Institute.

“Brain metastases are also very common in lung cancer and it would be very frustrating to have a patient with controlled brain disease excluded from a trial that could benefit them,” says Camidge, who has been intimately involved with the development of targeted therapies against non-small cell lung cancer, including crizotinib, alectinib and brigatinib. “Similarly, we have also started to see anecdotal evidence of new targeted therapies working against metastases in the brain, but current clinical trial design leaves holes in the data. For example, many trials don’t standardize capturing information on the use of prior radiotherapy in the brain and so in such cases it has been very hard to tell whether benefit in a patient’s CNS disease was due to radiotherapy or to the drug. When trying to choose between treatments, it was clear that we needed to get serious about demanding better data quality with respect to the brain.”

The new guidelines may be especially important for clinical trials addressing patients with cancer types that commonly spread to the brain, including non-small cell lung cancer, small cell lung cancer, HER2+ and triple-negative breast cancer, and melanoma, all of which become especially dangerous once reaching the central nervous system. In these conditions, the guidelines write that, “Exclusion of [brain metastasis] patients could remove half to two-thirds of the stage IV population.”

“We all hope that these guidelines will represent a turning point in cancer drug development,” Camidge says. “Over the next few years, changes in clinical trial design centered around generating and acting on early signals of a drug’s CNS activity or lack thereof should radically decrease risk and increase the therapeutic potential of new drugs across many different cancers.”

Tagged with:

About author

Related Articles