Are There Clinical Trials for Rare Cancers?

When someone has a rare cancer, they may have trouble getting more information after their diagnosis. They may also have a hard time finding a healthcare team with experience in treating the rare cancer.

Having a rare cancer can also mean fewer chances to join a clinical trial. But advances in how experts study and treat cancer are opening new doors. People with rare cancers now have better access to treatments that might not have been possible before.

“People with rare cancers face a world without standard treatment roadmaps, clear prognoses, or strong patient support networks. That’s why tumor-agnostic drugs and basket trials are so vital,” said Alberto Pappo, MD, an American Society of Clinical Oncology (ASCO) expert and pediatric oncologist at St. Jude Children’s Research Hospital.

How do clinical trials help?

Every new cancer medication must go through clinical trials before it can be approved for use in the United States. Clinical trials are studies that involve people. They test whether new medicines, procedures, devices, and other treatments are safe and work as intended.

“Clinical trials help cancer researchers develop new therapies faster,” said Brenda J. Weigel, MD, an ASCO expert and vice president of clinical research industry engagement at St. Jude’s.

Each clinical trial is carefully designed and conducted. All hospitals and doctors offering clinical trials follow the same rules for treating patients and tracking the study results. These rules make comparing data among the study patients easier. They also help ensure the study findings are accurate.

In the past, few trials studied rare cancers because not enough patients could take part. Smaller studies can make it hard to collect enough data about how well a treatment works.

“Healthcare providers, patients, and families often didn’t know what trials existed for rare cancers,” Dr. Weigel said. “Someone who wanted to join a clinical trial might have to travel long distances to places with expertise in those conditions.”

Taking a tumor-agnostic approach

New approaches to cancer research are expanding clinical trial opportunities for some people with rare cancers. These include tumor-agnostic therapies and basket trials.

Newer targeted therapies treat cancer by acting on specific features or genetic changes in cancer cells. These are called tumor-agnostic drugs because they can treat different types of cancer that have the same specific features or genetic changes.

Basket trials, also known as bucket trials, are research studies that test new drugs in people with the same genetic change. This study design allows people with rare cancers and those with more common cancers to take part in the same clinical trial. If the treatment is shown to be safe and effective, it can be approved to treat several different cancers with that genetic change.

“Tumor-agnostic basket trials have transformed cancer care and accelerated new targeted therapies,” said Dr. Pappo. “This is great news for people with rare cancers.”

Larotrectinib: A success story

For example, congenital infantile fibrosarcoma (CIFS) has benefited from the tumor-agnostic, basket-trial study design. CIFS is a rare cancer affecting only about 5 in every 1 million children. However, it is the most common soft tissue sarcoma diagnosed in children under 2 years old. Traditional treatment for CIFS has included surgery and, in some cases, chemotherapy. Because treatment happens so early in life, it can cause long-term side effects.

Nearly everyone with CIFS has a change in the NTRK gene. But several other cancers that affect children and adults can also have this same gene change. Using a basket-trial study design, researchers tested an NTRK inhibitor drug called larotrectinib in children and adults whose cancer has NTRK gene changes. The study included 17 different types of cancer, including CIFS. Study results showed that the treatment shrank tumors in 75% of patients. The treatment also prevented cancer from getting worse in about 55% of the patients for at least 1 year.

After these studies, larotrectinib became the second tumor-agnostic targeted therapy approved by the US Food and Drug Administration (FDA) based on basket trial results. Because larotrectinib targets a specific type of NTRK genetic change, it can be used to treat different types of cancer with this genetic change, including CIFS.

Having the option to use larotrectinib in children with certain rare cancers may allow some to avoid harsh chemotherapy and surgery. “Getting new cancer drugs to children early, in kid-friendly forms, was critical to the success of larotrectinib,” Dr. Pappo said.

How to find basket trials for rare cancers

If you’ve been diagnosed with a rare cancer, ask your doctor if a basket trial might be a good fit. Not every rare cancer has a genetic change that can be targeted with current therapies, so basket trials may not be an option.

“Your cancer care team can help determine whether you’re eligible to join a basket trial. If you are, they should be able to help you enroll in the study or connect you to the right people,” Dr. Weigel said.

You can also find support with clinical trials matching through ACS ACTS (Access to Clinical Trials & Support). The program helps you explore clinical trials options and connect with community resources.

Learn more from the American Cancer Society:

• Rare Cancers, Cancer Subtypes, and Pre-cancers
• Precision or Personalized Medicine
• Tumor-agnostic Drugs
• Phases of Clinical Trials

Dr. Pappo and Dr. Weigel are ASCO members.