Clinical Trial treatments are often the only hope for some cancer patients with advanced disease or complexities such as two types of cancer. However, strict guidelines for entering a clinical trial defined as “eligibility criteria”, exclude several patients desperately trying to enroll and access drugs that could lead to disease reduction and prolong life. A Washington Post article brings this issue to life by relating the stories of two such patients. Carly Bastiansen with pancreatic cancer, and Allen Lee with lung cancer. They have been rejected from several clinical trials on account of at least one of five eligibility criteria that need revamping; minimum age requirements for trial enrollment, HIV/AIDS status, brain metastases, organ dysfunction and a history of cancer or two concurrent cancer diagnoses.

The American society of clinical Oncology (ASCO) and the advocacy group Friends of Cancer Research issued recommendations published in November 2017, for broadening the above five eligibility criteria — minimum age requirements for trial enrollment, HIV/AIDS status, brain metastases, organ dysfunction and a history of cancer or two concurrent cancer diagnoses — that they identified as being most likely to restrict a patient's participation in a trial but least likely to affect their safety. Under those recommendations, the criteria that banned Bastiansen and Lee should be revisited.

Cancer Treatment Navigator (CTN) frequently helps Cancer patients navigate the complexities of clinical trial identification and enrollment. We also assist in gaining access to promising new cancer treatments outside of regular clinical trials. This is especially important when patients face a dead end because of overly stringent clinical trial enrollment processes. A re-examination of eligibility criteria is greatly welcomed as a positive step toward helping cancer patients with high unmet needs.

Photo Courtesy: Ingalls Cancer Care, Cancer Clinical Trials

More than 800 medicines and vaccines are being evaluated for cancer in clinical trial studies, or awaiting review by the U.S. Food and Drug Administration (FDA). Poor patient participation and under-enrollment in clinical trials remains a serious issue, but patients lacking an understanding of clinical trial design is equally important and needs education. Two concepts of clinical trial design, “clinical equipoise” and “randomization” are explored in this Medscape article, that presents the results of a survey administered to 1090 cancer patients (at 14 cancer centers in Ireland). The essence of these terms is captured below:

Clinical Equipoise: Uncertainty over the best treatment option when two are being compared in a clinical trial. The treating physician cannot ensure that a participant gets the “better” of the two treatments. For example, if an investigational drug is compared to an option acknowledged as the standard of care, it might turn out to be better or worse in terms of efficacy, safety or both.

Randomization: Treatment allocation is by chance. In the simplest trial design, one group receives the new treatment and is the investigational group. The other group receives standard therapy, and is the control group. At several points during and at the end of the clinical trial, researchers compare the groups to see which treatment is more effective or has fewer side effects. A computer is usually used to assign patients to groups.

At Cancer Treatment Navigator (CTN), we explain the nuances of cancer clinical trial methodology so patients can make an informed decision on participation. Understanding the above terms before signing consent is important and could impact a patient’s willingness to withdraw or remain in a clinical trial.

Understanding Randomization and Clinical Equipoise in Cancer Clinical Trials

The FDA approval for Kymriah (tisagenlecleucel, pronounced tis-a-gen-LEK-loo-sell) is a notable advancement in immunotherapy cancer treatments. Kymriah, a CAR T-cell gene therapy was approved for patients up to 25 years of age with B-cell precursor ALL (B-cell precursor lymphoblastic leukemia is a form of leukemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the blood and bone marrow. It is the most common type of acute lymphoblastic leukemia (ALL). Kymriah is intended for patients whose cancer has not responded to or has returned after initial treatment, which occurs in an estimated 15-20 percent of patients. How it works is that T-cells, a type of white blood cells that are the key players in our immune system, are removed from a patients' blood. They are re-programmed to carry new genetic material and injected back into the patient where they multiply and attack the cancerous leukemia. More details are in the FDA press release. The role patient testimonies played in an important FDA advisory panel, pre-approval meeting is of significance and is reported in this NYT news article.

Acknowledgement of Kymriah’s approval as a milestone for individualized cancer treatments was quickly followed by concern in the following areas:

1. High price ($475,000 for one treatment)
2. Safety (boxed warning of cytokine release syndrome, neurological events and infections)
3. Small eligible patient pool (CAR T-cell immunotherapies are highly anticipated by all cancer patients)

There are now 15+ immunotherapy agents approved by the FDA and 900+ being studied in clinical trials. This creates an enormous amount of information that is difficult to assess, not just for patients, but also their Oncologists. Media buzz around this promising class of cancer treatments further complicates the level of hope that should be maintained by cancer patients regarding their eligibility for the potentially life altering immunotherapy treatments. To solve issues around navigating information and decision-making, Cancer Treatment Navigator (CTN) works closely with a patient’s cancer care team to meticulously research treatments that have not yet been considered for a patient but could provide superior outcomes to existing approaches. Our recommendations are based on clinical science expertise. We compare evidence from publications to the diagnosis, treatment history and specific cancer type of each individual client, resulting in matches that are closely aligned to an individual’s disease and genetic mutation profile. This captures the essence of personalized medicine and makes it tangible for patients.

Emily Whitehead and her parents at the FDA Advisory Panel meeting. Photo Courtesy: T.J. Kirkpatrick, New York Times

Matching the right patient to the right treatment is the essence of what we do at the Cancer Treatment Navigator (CTN). A Guardian news article captures our approach of evaluating tumors based on site as well as specificity of mutations, and identifying treatments based on individual disease and genetic profile. Several cancers such as breast cancer and prostate cancer are treatable via personalized medicine in clinics and hospitals. But most have personalized medicine available largely in investigational clinical trial protocols. The CTN team considers cancer clinical trials as viable treatment options and researches the full array of approved and experimental therapies on an individual patient basis. This often results in recommending cancer patients treatments, that might not have been considered yet by their Oncologist. Bringing a personalized scientific arm to your cancer care team helps sort the hope from the hype.