The Cholangiocarcinoma Foundation has recently released a white paper titled “Cross-over arms in oncology clinical trials: An important consideration for patients.” This paper highlights a non-traditional clinical trial approach that could be more beneficial to patients that participate in them. Additionally, it could potentially encourage them to enroll in greater numbers, which would increase the quality of data in trials. Patient Worthy spoke with Stacie Lindsey, CEO of the foundation and a co-author of the paper, about the conclusions of the study.
About Cholangiocarcinoma
Cholangiocarcinoma is a form of cancer that affects the bile ducts. More specifically, the epithelial cells of the bile duct are the ones affected by this disease. The cause is not directly known; many patients who develop the disease also have no known risk factors, but there are some factors that are known to increase risk, such as primary sclerosing cholangitis, chronic liver diseases such as hepatitis, certain genetic disorders such as Caroli’s syndrome, infection with Helicobacter bacteria, and certain liver flukes, a type of parasitic animal that infiltrates the bile ducts and feeds on bile. Symptoms include fever, weight loss, jaundice, itching, and abdominal pain. Treatment may include surgery, chemotherapy, radiation, or liver transplant. Transplant is usually only useful if the disease is detected early; surgery is the best chance for curing cholangiocarcinoma. This disease is rapidly lethal if surgical removal is not possible. To learn more about cholangiocarcinoma, click here.
What is a Cross-Over Arm?
A vital case study used in this paper was the ClarIDHy study, which evaluated ivosidenib, a now-approved therapy, for certain cholangiocarcinoma patients. This study used a 2:1 randomization between the experimental drug arm and the control group arm. However, it allowed patients to cross-over from the standard of care arm into the experimental drug arm upon disease progression.
“In rare cancer trials, a placebo arm is unacceptable to patients, even being assigned to the standard of care arm is difficult when your standard of care is poor. Our suggestion for the protocol was that they allow patients to cross over into the experimental arm if they progressed on the standard of care arm.” – Stacie Lindsey, CEO, Cholangiocarcinoma Foundation
In diseases with very limited treatment options, including rare cancers like cholangiocarcinoma, clinical trials are increasingly being viewed as an active treatment option, not a last resort. As a result, trial models in which patients have a strong chance of receiving either no treatment (such as in a placebo group) or a poor standard of care are losing their appeal. This risk can make it more difficult to recruit patients, which inhibits trial effectiveness and diverse representation of the patient population.
Patients share perspectives on clinical trials at the foundation’s annual conference.
“The difficult thing about a cross-over arm is that the statistics are not ‘clean.’ You have patients crossing over from one arm to the other, so the data and outcomes do not look as statistically clear as they would if those two arms were completely independent. The FDA and other regulatory bodies want to see clean data. We want patients to have access to experimental drugs that may extend their quantity and quality of life. It was a good compromise.”
The paper was written as several other companies have developed interest in the inclusion of cross-over arms in trials. It details interactions with the company, clinicians and the FDA and the details of the model, as well as how it would function statistically, which would require innovations.
“It can’t be the statistics that keep the patients from getting access to experimental drugs that could save their lives or extend their quality of life.”
Check out the original paper and press release here.
