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

CAR T-cell therapies are one of the most promising and publicized immunotherapies, but limited in applicability. Two CAR T-cell immunotherapies approved by the FDA in 2017, Kymriah and Yescarta are limited to patients with specific types of blood cancer and failing prior conventional therapies. They are both designed for blocking a specific molecular target on cancer cells, either leukemia or lymphoma known as CD19. However, the CD19 molecule present on cancerous B cells is not the only one enabling them to multiply and grow. Rather, some patients with leukemia or lymphoma do not have CD19 on their cells, so the existing T-cell treatments do not work for them. Other patients, have CD19 at first and go into remission when treated, but then lose the protein and relapse within six months.

Researchers at the National Cancer Institute are engineering T cells to target the CD22 molecule (CD22-CAR) that is present on cancerous B cells, either in addition to CD19 or as the main driver of cancerous growth. This experimental therapy, if successful will provide an option to desperately ill leukemia patients who are relapsing on FDA approved CD19-CAR T-cell therapies. Additionally, it opens up the possibility of combination immunotherapy with two types of CAR T-cells administered simultaneously for enhanced results. These important developments are well covered in a New York Times Health article by author Denise Grady.

The Cancer Treatment Navigator team supports cancer patients in identifying the latest available treatment options and enabling access to targeted therapies and immunotherapies. Cancer patients often ask us about “Tumor melting T-cells”, described in press releases and news publications that highlight the breakthrough aspect, but often fail to explain the limitations of newly approved treatments. As scientific advisors to cancer patients, we explain nuances of approved immunotherapies and highlight experimental immunotherapies that might be more applicable to their specific cancer. Experimental immunotherapies require careful navigation given multiple clinical research trials running nationwide by hospitals and academic institutions. We encourage patients to leverage scientific research as part of their cancer care approach. Our team aims to emphasize balanced reviews and reports such as the New York Times article referenced above, so patients can be well educated and informed about cancer treatment choices.

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Photo: Cancer fighting T-cell attacking Leukemia cell from New York Times; Eye of Science, via Science Source

Cancer challenger, David Dunnington teamed up with Dr. Shailendra Bhatia at the Seattle Cancer Care Alliance (SCCA) toward initiating immunotherapy treatment to curb his cancer when he was running out of options. David had an uncommon Melanoma called acral lentiginous melanoma and his disease had spread after traditional chemotherapy and radiation therapy. David's tumors shrunk after a few doses of an immunotherapy that was in clinical trials at that time. David's key messages about cancer treatment navigation? He shared with Q13Fox reporter MARNI HUGHES that advocating for himself by researching and bringing ideas about treatment options, combined with a team that would listen to him is the key to effective outcomes. The video provides an impactful narrative from David and more details of the story are in the news article.

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