, by NCI Staff

SARS-CoV-2 virus particles (orange) isolated from a patient at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Credit: National Institutes of Health

In her spare time last year, Neelam Giri, M.D., joined an effort to test fellow NIH employees for SARS-CoV-2, the coronavirus that causes COVID-19. She administered the test to many employees with symptoms of COVID-19 in their cars outside the NIH Clinical Center in all kinds of weather.

For Dr. Giri, a staff clinician in NCI’s Division of Cancer Epidemiology and Genetics (DCEG), the testing was volunteer work. And in December, she became one of the first frontline workers at the Clinical Center to receive the Moderna COVID-19 vaccine.

“I’m honored to be part of this campaign to end the pandemic,” Dr. Giri said before receiving the vaccine at an event to kick off COVID-19 vaccinations among NIH employees. Her volunteer job illustrates one of the many ways that cancer researchers have been working against COVID-19.

Since the pandemic began, cancer researchers have also been contributing their expertise and resources to scientific investigations of the coronavirus. Their findings have been broad in scope, ranging from insights into how the virus enters cells to the identification of potential therapies.

For example, cancer researchers reported recently that antibodies to SARS-CoV-2 may protect people from being reinfected by the virus. The research was part of NCI’s ongoing response to the pandemic, which also includes a study of patients with cancer and COVID-19 and studies of genomic factors that influence the severity of the disease.

As the pandemic continues, the results of these and other studies could inform the prevention and treatment of COVID-19 among individuals with and without cancer, according to cancer researchers who have investigated SARS-CoV-2.

“Many cancer researchers have been able to pivot portions of their research—either in the laboratory or in the clinic—to try to better understand COVID-19 and find ways to treat the disease,” said James Gulley, M.D., Ph.D., head of the immunotherapy section of NCI’s Center for Cancer Research (CCR).

Cancer researchers are well suited to investigate COVID-19 “because we are used to dealing with complex biological problems,” Dr. Gulley continued. And some of the tools used to study how the immune system interacts with tumors can be modified to study SARS-CoV-2, he added.

Testing Biomarkers for the Severity of COVID-19

Last spring, for example, several cancer researchers in New York City shifted their focus from studying immunotherapy—treatments that help the immune system to detect and kill cancer cells—to investigating the body’s response to the coronavirus.

Sacha Gnjatic, Ph.D., of the Icahn School of Medicine at Mount Sinai and his colleagues identified proteins called cytokines that could be indicators, or biomarkers, of the severity of COVID-19 and the response to treatment. Increased blood levels of two cytokines—IL-6 and TNF-a—were associated with poor survival and severe forms of COVID-19 in a large group of hospitalized patients.

The results suggested that these cytokines could potentially guide decisions about the type of care that people with COVID-19 should receive, Dr. Gnjatic said. “Such biomarkers could be evaluated in future clinical trials,” he added.

About 10% of the patients with COVID-19 in the study also had cancer. “We are still analyzing the data to see whether there are certain factors that make these patients more likely to develop severe COVID-19 than other patients,” said Dr. Gnjatic.

He brought to the project his experience leading an NCI-sponsored initiative to develop biomarkers that doctors could use to identify patients with cancer who are likely to respond to immunotherapy drugs.

“We are interested in the interplay between tumors and the immune system,” said Dr. Gnjatic. “When COVID-19 hit, we were primed to use our research methods to investigate the pathology of the disease.”

Starting in March, Dr. Gnjatic co-led a team of researchers at Mount Sinai Hospital that created a COVID-19 research biobank. In just two months, the biobank collected blood samples from 500 patients hospitalized with COVID-19. Since then, the biobank has added samples from nearly 300 hospitalized patients, and all of these patients have been followed over time.

“We now have at least 6 months of follow-up data,” Dr. Gnjatic said. “The biobank will allow us to analyze many more biomarkers, predict patient outcomes, assess the impact of treatment, and hopefully contribute to better clinical care of patients with COVID-19.”

Investigating COVID-19 in People with Cancer

Researchers have reported that people with cancer may be at an increased risk of developing more serious forms of COVID-19.

“The prior therapies that patients with cancer have had may make them more likely to get sick from COVID-19,” said Nirali Shah, M.D., of CCR, who co-led a clinical trial testing the drug tocilizumab (Actemra) in patients with cancer and COVID-19. Cancer and certain treatments for cancer, she noted, can weaken the immune system.

Patients with cancer also tend to be older and may have risk factors linked to aggressive forms of COVID-19, noted Ziad Bakouny, M.D., of the Dana-Farber Cancer Institute, who coauthored a recent overview of cancer and COVID-19. These risk factors include certain underlying health conditions, such as diabetes and a heart condition.

“In general, patients with cancer have more severe COVID-19 symptoms at diagnosis and, unfortunately, they also have worse outcomes than patients who don’t have cancer,” Dr. Bakouny said.

More research, he continued, is needed to understand “how the biology of cancer and COVID-19 may interact in individuals with both diseases.”

Some answers may come from the NCI COVID-19 in Cancer Patients Study (NCCAPS). In this natural history study, researchers are collecting data, blood samples, and images from people with cancer and COVID-19. Participants will provide blood samples at multiple time points over a 2-year period.

“We expect that the samples and data we are collecting will help researchers to better understand many aspects of how COVID-19 is affecting patients with cancer,” said Larissa Korde, M.D., of NCI’s Cancer Therapy Evaluation Program and a leader of the NCCAPS study.

The researchers have been enrolling children and adults at some 700 sites across the country, including sites that are part of the NCI Community Oncology Research Program (NCORP). NCORP reaches patients in underserved areas, many of which have been disproportionately affected by the pandemic.

The results will complement findings from the COVID-19 and Cancer ConsortiumExit Disclaimer, a research study involving 125 hospitals across the country that is collecting data about people diagnosed with COVID-19 and cancer, noted Dr. Korde.

Revealing Clues to Coronavirus Infections and Treatment Possibilities

Some cancer researchers, including DCEG’s Ludmila Prokunina-Olsson, Ph.D., have focused on the underlying biology of coronavirus infections.

Last fall, her team described a previously unknown form of ACE2, the receptor protein used by the coronavirus to bind to and infect cells. The newly identified molecule—now called deltaACE2 (dACE2)—is shorter than the other form of ACE2 and does not appear to bind to SARS-CoV-2, which means that it is unlikely to be a gateway for viruses to enter human cells, said Dr. Prokunina-Olsson.

The researchers also found that certain cells, including some tumor cells, produce dACE2 when exposed to interferons. The body makes interferons in response to viral infections; interferons are also synthetically produced as drugs to treat cancer, infections, and other diseases. In clinical trials, researchers have been testing interferons as possible treatments for COVID-19.

In their study, Dr. Prokunina-Olsson and her colleagues found that the full-length ACE2 protein did not appear to be produced by cells in response to exposure to interferons or viruses, as some previous studies had suggested.

Taken together, the new findings suggest that exposure to viruses or interferons used for treatment may lead to the expression of dACE2 rather than the full-length form of the ACE2 receptor—and would therefore not increase the risk of cells being infected by SARS-CoV-2.

Two other groups of researchers recently confirmed the existence of dACE2 in human cells. “We are conducting additional experiments to understand why and when dACE2 is produced by normal and tumor cells—and whether differences in the expression of ACE2 and dACE2 could be important for infection,” said Dr. Prokunina-Olsson.

Profiling T-Cell Responses to the Coronavirus

Cancer researchers have also been investigating the body’s response to SARS-CoV-2, including the role that immune cells called T cells may play in fighting the infection.

“T cells can identify cells that have been infected by the virus and kill those cells,” said Dr. Gulley. “We think that studying T cells will be important for understanding the immune system’s response to SARS-CoV-2 as well as the immune response to vaccines against the virus.”

In cancer immunotherapy research, investigators routinely monitor how T cells are turned on, or activated, in response to certain proteins (antigens) on tumor cells. “We can bring this experience to the fight against COVID-19,” said Dr. Gulley.

Some of Dr. Gulley’s colleagues in CCR have done just that. A team led by Jeffrey Schlom, Ph.D., and Renee Donahue, Ph.D., has adapted tests used to profile T-cell responses to tumor antigens for studies of the coronavirus.

“As COVID-19 emerged, we modified the tests so that we could specifically measure T-cell responses against certain parts of the coronavirus, such as the spike protein on the surface of the virus and the nuclear protein,” said Dr. Donahue, of the Laboratory of Tumor Immunology and Biology.

The new technology “offers a very sophisticated way of looking at T cells and determining how active they are against certain viral proteins,” said Dr. Gulley.

The tests could be used to study COVID-19 vaccines in patients with cancer who are receiving immunotherapy, noted Dr. Donahue. “We need to learn whether COVID-19 vaccines can generate effective immune responses in patients being treated for cancer,” she added.

Understanding Inflammatory “Storms”

In some patients with severe COVID-19, the immune system mounts an overly aggressive response to the virus. When this happens, the body may produce large numbers of cytokines. By stimulating the immune system, these proteins can damage vital organs, such as the lungs and the heart, leading to death. This hyperinflammatory state is sometimes called a cytokine storm.

Uncontrolled immune responses involving cytokines can also occur in patients with cancer who receive immunotherapy drugs known as CAR T-cell therapies. In these patients, the phenomenon—called cytokine release syndrome—occurs when large amounts of cytokines are released into the blood all at once.

Such responses can be life-threatening, so patients receiving immunotherapy are routinely monitored for evidence of aggressive immune responses and treated as needed.

Although some of the same cytokines may be involved in responses to CAR T-cell therapy and to the coronavirus, the underlying biology of these responses is different, Dr. Shah explained.

“Fundamentally, what is happening with COVID-19 is that an infection leads to an inflammatory response,” said Dr. Shah.

“There may be direct or indirect injury to tissue as a result of COVID-19, and this could lead to very different immune responses,” she continued. “Also, for a host of reasons, some patients may have more of an inflammatory response than others.”

Understanding why people can have such different responses to infection with the coronavirus is the focus of ongoing investigations. For example, the NIH-led COVIDcode study is examining how genetic variants may contribute to the severity of COVID-19.

Testing Potential Treatments for COVID-19

Cancer researchers have also played a role in identifying and evaluating potential treatments for overactive immune responses associated with COVID-19. Several cancer drugs—or drugs being studied as cancer treatments—have been evaluated for this purpose.

“The results of these studies have been mixed, and more research is needed to determine which treatments may be effective,” said Dr. Bakouny, who noted that certain steroids have been shown in clinical trials to treat overactive immune responses associated with COVID-19.

One of the first cancer drugs to be evaluated for COVID-19 was acalabrutinib (Calquence). This treatment blocks the activity of a protein called Bruton’s tyrosine kinase (BTK), which plays an important role in the normal immune system.

Last March, a team led by Wyndham Wilson, M.D., and Louis Staudt, M.D., Ph.D., in CCR launched a small study to test acalabrutinib in 19 patients hospitalized with severe COVID-19.

The researchers had conducted the studies that led to acalabrutinib’s approval for certain types of lymphoma and leukemia. Some of this research had suggested that BTK inhibitors could impair the body’s immune response.

“We took the knowledge we had about the drug from our cancer studies and tried to apply that to the treatment of patients with COVID-19 who had the most dramatic immune responses,” said NCI’s Mark Roschewski, M.D., who helped conduct the study.

In the study, some of the 19 patients seemed to benefit from the drug. But in a subsequent randomized clinical trial, the drug did not improve the number of patients who were alive and free of respiratory failure, according to the maker of acalabrutinib, AstraZeneca.

Nonetheless, the research on BTK inhibitors that began during the pandemic will continue through a study called RESPOND, which is led by the National Institute of Allergy and Infectious Diseases.

“What we learn may help us understand how these inhibitors could potentially be useful for the treatment of other common inflammatory and autoimmune conditions that afflict the general population,” said the study’s lead investigator, Michail Lionakis, M.D., Sc.D., who also collaborated on the NCI-led acalabrutinib research.

An Unprecedented Pace of Scientific Discovery

Researchers have been studying coronaviruses for decades, Dr. Gulley noted, so investigators “already have a head start on identifying important questions to explore.”

He added, “The more research tools we can bring to this fight—and the more different angles we can come at this virus—the better our chances of gaining insights that will help us to more effectively treat the virus and limit its spread.”

Dr. Prokunina-Olsson said that the pace of scientific discoveries related to COVID-19 has been “unprecedented.” She undertook her study of ACE2 in response to research that had been posted online for the scientific community early in the pandemic.

The practice of sharing scientific results almost in real time fuels new studies and raises additional research questions, Dr. Prokunina-Olsson stressed.

“This process has allowed the research community to conduct follow-up studies and to refine the messages of previous publications,” she said. “What could normally take several years happened in a matter of months.”

Frequently Asked Questions About CCR Clinical Trials

What are cancer clinical trials? Why are they important?

What are some possible benefits of clinical trial participation?

What are some possible risks of clinical trial participation?

What kinds of treatment can I expect to receive in a clinical trial?

Is there a chance I might receive a placebo or sugar pill?

Who can participate in cancer clinical trials?

Q. What are cancer clinical trials? Why are they important?

A. Cancer clinical trials are conducted in hopes of finding better ways to prevent and treat cancer. Clinical trials answer important scientific questions, which can lead to future advances in care. Most of today’s standard treatments are based on previous clinical trial results. Because of the progress made in clinical trials, many people with cancer are living longer. In addition to improved survival rates, clinical trials have contributed to:

  • Lower recurrence rates for many cancers
  • New treatment approaches for cancers that had no effective therapy
  • Fewer side effects from treatment
  • Better quality of life for people with cancer

Q. What are some possible benefits of clinical trial participation?

A. Possible benefits:

  • Treatment trials offer the most advanced innovations and scientific thinking in cancer care
  • If a new treatment or prevention drug or regimen is successful, trial participants may be the first to benefit from it
  • Many people derive an emotional benefit from taking part in a trial that may help others who have cancer

Q. What are some possible risks of clinical trial participation?

A. Possible risks:

  • New treatments being studied are not always more effective than standard care. They may have similar or less effective results
  • Even when a new treatment or prevention approach has benefits, not every patient who receives the treatment will experience them
  • New treatments or prevention approaches may have unexpected side effects or risks
  • The trial may impose difficulties on lifestyle, such as getting transportation to the trial site, time off from work, and child care

Q. What kinds of treatment can I expect to receive in a clinical trial?

A. The National Cancer Institute (NCI) trials use several types of treatment and prevention methods:

  • Antiangiogenesis: therapy that uses drugs to block the growth of new blood vessels to a tumor, cutting off the tumor’s supply of oxygen and nutrients
  • Bone marrow transplantation: procedure that replaces bone marrow destroyed by high doses of anticancer drugs or radiation treatments
  • Chemotherapy: treatment with anticancer drugs
  • Hormone therapy: treatment that adds, blocks, or removes hormones to halt or limit cancer cell growth
  • Immunotherapy: treatment to stimulate or restore the ability of the immune system to fight infection and diseases, also called biological therapy, biotherapy, or biological response modifier therapy
  • Monoclonal antibodies: laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body; each of the many monoclonal antibodies recognizes a different protein on certain cancer cells; monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor
  • Radiation therapy: use of X-rays, neutrons, and other sources of high-energy radiation to kill cancer cells and shrink tumors
  • Surgery: removal of a cancerous growth through an operation
  • Vaccine: a substance or group of substances meant to cause the immune system to respond to a tumor or disease; a vaccine can help the body recognize and destroy cancer cells

Q. Is there a chance I might receive a placebo or sugar pill?

A. Placebos (i.e., sugar pills) are rarely used in cancer treatment trials. No one is ever given a placebo when an effective treatment is available to treat his or her cancer. In very rare cases, a placebo may be used when testing a new drug if there is no known effective treatment for the specific cancer type or stage. If a trial does use a placebo, patients are always informed before taking part in the trial.

Q. Who can participate in cancer clinical trials?

A. Anyone who meets the eligibility requirements can participate. U.S. citizens and permanent residents are given first priority.

Source: National Cancer Institute

Health Insurance Coverage of Clinical Trials

Approved by the Cancer.Net Editorial Board, 10/2018

Understanding the costs covered by insurance

The Patient Protection and Affordable Care Act (ACA) is a federal law that regulates health plans and insurance coverage. It is a type of health care reform.

This law includes regulations regarding insurance coverage of clinical trials. Specifically, the ACA states that health plans or insurers cannot:

  • Keep patients from joining a clinical trial.
  • Limit or deny coverage of routine costs to patients who join an approved clinical trial.
  • Increase costs because a patient joins a clinical trial.

The clinical trials coverage provision does not apply to “grandfathered” health plans. These plans existed on or before March 23, 2010, the date that the ACA went into effect.

But if a plan has reduced benefits or raised costs since the ACA went into effect, the government may no longer consider it a grandfathered plan. Losing grandfathered status means the plan must follow all ACA requirements. This includes covering routine clinical trial costs.

A grandfathered plan must note its grandfathered status in materials that describe the plan benefits. If you do not know if your plan is considered a grandfathered plan, contact your health insurance provider.

Approved clinical trials

The law applies to clinical trials designed to study new methods to prevent, detect, or treat cancer or another life-threatening illness. According to the law, an approved clinical trial must meet any of the following conditions:

Be federally approved or funded. This means 1 or more of the organizations listed below approved or funded the clinical trial.

  • National Institutes of Health (NIH), including organizations under NIH such as the National Cancer Institute (NCI)
  • Organizations funded by the NIH or NCI, including academic institutions, designated cancer centers, and cooperative groups
  • Centers for Disease Control and Prevention (CDC)
  • Agency for Health Care Research and Quality (ARHQ)
  • Center for Medicare and Medicaid Services (CMS)
  • Department of Defense, Department of Veteran Affairs, or the Department of Energy, if the trial is subject to unbiased, scientific review that is similar to NIH requirements

Have an investigational new drug application. Research regulated by the U.S. Food and Drug Administration (FDA) must include an investigational new drug application. Researchers need FDA approval to provide a drug that is still under development in a clinical trial. Your doctor or the clinical trial sponsor can tell you if the study has approval for an investigational new drug.

Be excused from investigational new drug application requirements. Sometimes, researchers do not need to ask the FDA for permission. This occurs when drug makers are not looking to include a new use of an existing drug in the labeling or advertising. But researchers still need the FDA to approve changes to a drug’s labeling or advertising. Researchers also need FDA approval to test changes in drug dose or ways to give a drug if it can increase risk for the people participating.

Your doctor can help determine if the ACA covers the clinical trial you are considering.

Routine costs and choice of provider

If you choose to join a clinical trial and the ACA requirements apply to your insurance plan, your insurer must cover routine costs. Examples of routine costs include:

  • Office visits
  • Lab tests
  • Supportive care drugs
  • Procedures and services you need while you are in the trial

These are costs your insurer would cover even if you were not in the trial. But your insurer does not need to cover the treatment being studied. (See “Costs not covered,” below)

Additionally, your insurer may not cover health care providers outside your health plan’s network. The insurance materials should list the providers covered by your plan.

Sometimes an insurance plan includes coverage for out-of-network providers. These are doctors and hospitals that the insurer does not list as part of its network. If you have out-of-network coverage, the insurer must cover your routine costs of care for a clinical trial with a provider outside your network.

Medicare and Medicaid coverage

Medicare. The ACA does not affect Medicare coverage of clinical trial costs. Medicare has slightly different rules for covering clinical trials.

Medicare covers the following routine clinical trial costs:

  • Drugs, procedures, and services that Medicare would cover if you were not enrolled in the clinical trial.
  • Medical care needed for the treatment that the clinical trial is studying. For example, Medicare would cover medical care related to chemotherapy. But it would not cover the new chemotherapy drug.
  • Medical care related to health problems from the clinical trial. One example is the prevention and management of side effects.

Special rules apply for people enrolled in Medicare-managed care plans. These plans are also called Medicare Advantage plans.

If you are in one of these plans, traditional Medicare covers routine costs of the clinical trial. Then, the Medicare Advantage plan pays any difference in your out-of-pocket costs between traditional Medicare and the Medicare Advantage plan.

Medicare does not cover research-related costs.

Medicaid. The ACA clinical trials coverage rule does not apply to Medicaid plans. Federal law does not require states to cover clinical trials through Medicaid. But some states have laws that require Medicaid to cover clinical trials. Learn more about insurance coverage of clinical trials by state. Please note that this link takes you to a different ASCO website.

Costs not covered by health insurance

It is important to know which costs you will need to pay before joining a clinical trial. Remember, health insurance companies and Medicare are not required to cover:

  • The cost of the treatment or procedure the clinical trial is studying
  • Any procedure only needed to collect data for the study

Talk with the clinical trial research team about what your insurance plan may cover. And check if your insurance plan must meet the ACA clinical trial coverage requirements. You will usually talk about this with the research team during the informed consent process.

Find more information about cancer clinical trials near you HERE.

ASCO and Friends of Cancer Research Recommend Expanding Patient Access to Cancer Clinical Trials by Further Broadening Eligibility Criteria

from www.ASCO.org
February 9, 2021


Working to broaden clinical trial eligibility criteria ASCO and Friends of Cancer. SCORThe American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) jointly issued new recommendations to further efforts to broaden eligibility criteria in cancer clinical trials with the goal of making clinical trials more accessible to patients. The joint recommendations are detailed in a series of articles published in Clinical Cancer Research, a journal of the American Association for Cancer ResearchThe series provides a comprehensive examination of eligibility criteria for cancer clinical trials with recommendations to address five specific areas: treatment washout periods, concomitant medications, prior therapies, laboratory reference ranges and test intervals, and patient performance status.

“Clinical trial access must be recognized as a health equity issue. Overly restrictive eligibility criteria without scientific justification has led to an underrepresentation of older adults, racial/ethnic and sexual/gender minorities, and patients with well-managed comorbidities,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO. “We’re proud to continue our collaboration with Friends of Cancer Research to make eligibility criteria less restrictive so that clinical trial populations can be more inclusive and representative of cancer patient populations and improve results for all patients.”

Trial eligibility criteria are designed to protect participant safety and define an appropriate study population. However, overly restrictive eligibility criteria can limit the participation of patients in a clinical trial who share critical characteristics with those likely to be treated based on the study’s results. These restrictions make it hard for clinicians to fully understand how a more diverse patient population typically seen in clinical practice will respond to a therapy post-approval. Overly restrictive eligibility criteria can also reduce patient access to potentially life-prolonging novel treatments and slow down the generation of research results. Using recommendations made by ASCO and Friends in 2017, a new analysis of data from CancerLinQ Discovery® (CancerLinQ’s deidentified real-world data product for researchers) found that expanding just three common eligibility criteria—renal function measures, presence of brain metastases, and history of prior malignancy—increases the percentage of lung cancer patients potentially eligible for clinical trials almost twofold.

To address this issue, ASCO and Friends worked with stakeholders throughout the cancer research community to develop evidence-based, consensus recommendations that are focused on expanding eligibility criteria to make trial populations more reflective of the general cancer population, reduce clinical trial complexity, and exclude patients from trials only where it is warranted due to safety concerns. Implementation of the recommendations, ASCO and Friends assert, can expedite patient recruitment, accelerate learning, decrease trial ‘failure rate’ due to slow enrollment, increase opportunities for patient participation and benefit, and make trial results more generalizable to the population that would use the treatment in routine clinical care.

“As new cancer therapies are being developed, we must think broadly about how eligibility criteria are determined.” said Jeff Allen, PhD, President & CEO of Friends of Cancer Research. “We need to find an optimal balance between improving patient access to clinical trials and the methods used for robust evaluation of safety and efficacy of new therapies. Modernizing eligibility criteria for enrollment will bring more trials to more patients, and ultimately help inform the optimal use of new medicines more quickly.”

The recommendations published today were developed by stakeholders from ASCO, Friends, academic and community research sites, the Food and Drug Administration (FDA), National Cancer Institute (NCI), patient advocates and advocacy groups, NCI National Clinical Trials Network Groups, and the pharma-biotech industry.

New Recommendations Build on Ongoing Work to Expand Eligibility Criteria and Simplify Trial Operations

In 2016, ASCO, Friends, and FDA formed a collaboration to address overly restrictive cancer clinical trial eligibility criteria. Project leadership selected five criteria that commonly lead to the exclusion of specific patient populations from clinical trials (brain metastases, minimum age for enrollment, HIV status, organ dysfunction, and prior or concurrent malignancies) and tasked multi-stakeholder working groups with recommending less restrictive eligibility criteria addressing these five factors. An ASCO-Friends Joint Research Statement and supporting working group papers were published in the Journal of Clinical Oncology in 2017.

As a result of efforts by ASCO and Friends to disseminate and encourage implementation of those recommendations, in September 2018 NCI revised protocol template language based on the recommendations, stating that the updated criteria should be implemented where possible in active protocols and included in future Experimental Therapeutics Clinical Trials Network and National Clinical Trials Network trial protocols. Additionally, in July 2020, FDA released four final guidance documents recommending broadening eligibility criteria related to brain metastasesHIV and Hepatitis B/C infectionsorgan dysfunction and prior/concurrent malignancies, and minimum age requirements.

ASCO and Friends will continue to work closely with FDA, NCI, trial sponsors, institutional review boards (IRBs), contract research organizations (CROs), and patient groups to disseminate the latest recommendations, share analyses, and help to successfully implement changes in protocols to broaden eligibility criteria appropriately.

More detailed information on each article is provided below. 


ASCO-Friends Joint Research Statement

Overview: This article provides an overview of the ASCO and Friends eligibility criteria initiativeoutlines goals and rationale, and describes the process used to develop the recommendations. The article also provides a summary of the working groups’ recommendations.

Washout Periods and Concomitant Medications

Background: Washout periods for prior treatments and interventions limit timely accrual and may prevent patient enrollment without adding safety measures or preventing misinterpretation of efficacy results. Excluding patients who require concomitant medications (other medications taken by the patient that are unrelated to the investigational treatment) for other illnesses or supportive care management limits understanding of the investigational agent’s tolerability and dosing in those likely to receive the treatment post-approval and excludes many older patients with co-morbid illnesses.

This working group recommends the use of less restrictive requirements for prior therapy washout periods and concomitant medication in most instances. Specifically:

  • Time-based washout periods should be removed from protocol eligibility criteria in most cases.
  • Relevant clinical and laboratory parameters should be used in place of time-based washout periods to address safety considerations.
  • Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
  • Concomitant medications use should only exclude patients from trial participation when clinically relevant known or predicted drug-drug interactions or potential overlapping toxicities will impact safety or efficacy.

Performance Status

Background: Performance status (PS) is one of the most common eligibility criteria, often limiting clinical trial populations to highly functional and minimally symptomatic individuals who do not reflect the populations afflicted with the disease. Existing PS tools are inherently subjective and invite bias, and PS does not reliably predict outcomes for older adults.


  • Patients with reduced PS should be included unless there is a scientific and/or clinical rationale for exclusion justified by established safety considerations. PS eligibility criteria should be continually re-evaluated and modified throughout the clinical development process to reflect accumulated safety data of the investigational treatment.
  • Investigators should consider alternate trial designs, such as pre-specified cohorts with lower PS that are exempt from the primary analysis, to encourage inclusion of these patients.
  • Investigators should consider additional assessments to better characterize the functional status of ECOG PS2 patients and patients aged ≥65.

Laboratory Tests

Background: Laboratory test-related eligibility criteria may exclude a significant portion of patients from clinical trials unnecessarily and can have disproportionate impact on patients according to age, gender, race, and ethnicity.

The proposed recommendations help guide appropriate use of laboratory tests and testing intervals to safely enable increased clinical trial accrual and provide more relevant data that better mirror oncology patient populations. Specifically, the article recommends:

  • Laboratory test results should only be used as exclusion criteria when scientifically justified and when abnormal test results confer safety concerns.
  • Laboratory reference values should account for potential normal variations due to race, ethnicity, age, sex, and gender identity.
  • Routine re-assessment of laboratory test-based exclusion criteria should be conducted during the course of clinical research and drug development.
  • Investigators should consider increasing the intervals between protocol-specified tests to help reduce patient burden and rely more on routine clinical testing.

Prior Therapies

Background: A patient’s prior therapies—including number or type—are often used either as exclusion or inclusion criteria for enrollment into clinical trials.

The multi-stakeholder working group has recommended:

  • Patients should be eligible for clinical trials regardless of the number or type of prior therapies and without a requirement to have received a specific therapy prior to enrollment unless there is a scientific or clinical rationale.
  • Prior therapy could be used to determine eligibility in the following cases:
    • If the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy.
    • If the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory.
    • In randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received.
  • Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies.

CancerLinQ Discovery Analysis

Overview: An analysis of real-world data from the CancerLinQ® Discovery database shows that expansion of three common eligibility criteria—renal function measures, presence of brain metastases, and history of prior malignancy—increases the number of patients with lung cancer in the dataset analyzed who are potentially eligible to enroll in a trial almost two-fold. This analysis was conducted in a population with advanced non-small cell lung cancer, although the paper suggests that the findings are likely applicable to other advanced malignancies.

Colorectal Cancer: Latest Research

March is Colorectal Cancer Awareness Month, clinical trials, research, study. SCORDoctors are working to learn more about colorectal cancer, ways to prevent it, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Always talk with your doctor about the best diagnostic and treatment options for you.

  • Improved detection methods. Researchers are developing tests to analyze stool samples to find genetic changes associated with colorectal cancer. By finding and removing polyps or identifying cancer early, doctors have a better chance of curing the disease.
  • Tests to predict the risk of cancer recurrence. Various genes play important roles in the growth and spread of tumors. Tests to identify these genes can help doctors and patients decide whether to use chemotherapy after treatment. Researchers hope that these tests can help people with a lower risk of recurrence avoid the side effects of additional treatment.
  • Immunotherapy. In the past several years, researchers have discovered a class of drugs that targets the ways that tumor cells avoid the immune system. These drugs are called checkpoint inhibitors. The latest research has shown that certain checkpoint inhibitors, called PD-1 or PD-L1 inhibitors, can be effective against a type of metastatic colorectal cancer that is microsatellite high (MSI-H). There are ongoing clinical trials looking at combining checkpoint inhibitors with other drugs or cancer-directed treatments to see if they can be helpful in tumors that are not MSI-H.
  • BRAF mutationsBRAF genetic mutations occur in about 10% of colorectal cancers. For cancers that metastasize, there are clinical trials testing targeted therapies aimed at BRAF-mutated tumors. Studies have found certain combination therapy strategies that may work on BRAF-mutated tumors.
  • New drugs. Many new drugs are being tested for colorectal cancer, including advanced colon and rectal cancers. New types of chemotherapy and targeted therapy are being studied. Most are only available through clinical trials.
  • Palliative care/supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current colorectal cancer treatments to improve comfort and quality of life for patients.

For more information about colorectal cancer clinical trials in your area, click HERE.

Source: www.cancer.net