Study defines clinical trials likely to exclude patients with brain metastases

September 9, 2015

Non-small cell lung cancer frequently spreads to the central nervous system (CNS), but patients with CNS metastases may be excluded from clinical trials of new drugs. A University of Colorado Cancer Center study being presented at the 16th World Conference on Lung Cancer reveals the full extent to which the CNS may be under-explored in clinical research.

The study combed the website ClinicalTrials.gov to identify 413 open lung cancer . Overall, 41 percent of only included patients if their CNS disease was previously treated. Twenty-six percent allowed in patients with CNS involvement and no previous treatment. Fourteen percent excluded all patients with a history of brain spread and nineteen percent of trials did not comment on any criteria related to CNS disease at all.

When multiple different subcategories of clinical trial were considered, only the sponsor of the trial was significantly associated with strict CNS exclusion, with university-sponsored trials being significantly less likely to exclude such patients than industry-sponsored trials (Hazard Ratio 0.442, p=0.0342).

"On one hand, if a new drug works great in the rest of the body but somehow doesn't get into the brain, including patients with untreated brain metastases could put the patients at increased risk as well as lower the initial estimates of the drug's activity," says Caroline McCoach, MD, PhD, investigator at the CU Cancer Center and the presenting author of the study. "But on the other hand, if we fail to include patients on the trial of a drug that does work in the brain, we may not discover the drug's activity for a long time and patients who may benefit would be inappropriately excluded."

"The fact that the only dominant factor affecting strict exclusion was the sponsor of the trial suggests that some of our current practice may be based more on habit, than perhaps universally agreed upon scientific rationale," says D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the CU Cancer Center and senior author of the study.

Indeed, in the last two years, the Response Assessment in Neuro-Oncology (RANO) group, an assembly of international experts, have been driving a series of publications that have started to build a more rational approach to addressing brain metastases in clinical trials.

"Dr. McCoach's presentation really defines the status quo for how patients with CNS disease are being treated in clinical trials and has already started a lot of debate within the RANO group," Camidge says.

"What we really want to see are sensible clinical trial designs, with CNS inclusion and exclusion criteria that are logical and appropriate given both what is or isn't known about the drug's activity in the brain and how far advanced an experimental drug is in development at the time," says Camidge. "In an ideal world that might well involve dedicated clinical trial sub-studies looking at patients with untreated CNS disease very early in drug development, trying to see if there is a CNS signal to explore further, or modify later trials to more appropriately manage risks if the drug is unlikely to work in the CNS."

"Sometimes, we may have to learn by mistakes," says McCoach explaining that many trials of the new class of immunotherapy drugs completely excluded patients with yet newer data seems to show that CNS responses can safely occur and this early caution and denial of trial access to such may not have been warranted.

"The brain is an important battleground for treatment right now, and you can't really force the issue of wanting better trial designs until you show people the lack of consensus in how we are currently doing things. The goal of this study was to highlight the full extent of current practice and open up the field for more informed debate," she says.

Explore further: Promising trial of brigatinib shows all next-gen ALK inhibitors may not be created equal

Related Stories

Promising trial of brigatinib shows all next-gen ALK inhibitors may not be created equal

May 27, 2015
Phase I/II clinical trial results reported at the American Society for Clinical Oncology (ASCO) Annual Meeting 2015 show promising results for investigational drug brigatinib against ALK+ non-small cell lung cancer (NSCLC), ...

Preclinical tests may lead to new approach to treat CNS lymphoma

August 12, 2013
A drug recently approved for use in multiple myeloma is now being tested for its ability to fight central nervous system (CNS) lymphoma, a deadly cancer of the immune system that can affect the brain, spinal cord and fluid, ...

Study defines criteria for MET-driven lung cancer suitable for crizotinib treatment

September 8, 2015
Many cancers include increased copies of the gene MET. But in which cases is MET driving the cancer and in which do these increased copies happen to "ride along" with other molecular abnormalities that are the true cause ...

Patients don't understand the purpose of clinical drug trials

August 17, 2015
Clinical trials are an important part of cancer research. Future patients depend on the severely ill to test drugs to improve treatment. But in her dissertation from Uppsala University, Tove Godskesen shows that some of these ...

Study finds no reason for cancer survivors to be excluded in advanced stage lung cancer trials

February 9, 2015
The common practice of excluding patients with a prior cancer diagnosis from lung cancer clinical trials may not be justified, according to a study by researchers from UT Southwestern Medical Center.

Benefit of targeted lung cancer therapy confirmed

June 3, 2011
A drug that targets a specific type of lung cancer shows a dramatic response in more than half of the people who take it. The drug, called crizotinib, has been in clinical trials since 2006, and the results from the largest ...

Recommended for you

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.