New Therapies for Children With Solid Tumors

As new, more targeted cancer therapies for adults are approved by the U.S. Food and Drug Administration (FDA), researchers are turning their focus to drugs that attack solid tumors in children.

The idea behind targeted therapies is that the drugs attack tumor cells directly. For example, one way targeted therapies function is to prevent tumor cells from forming new blood vessels that could fuel tumor growth. Essentially, they work to starve growing tumors.

Other targeted therapies inhibit specific proteins that sit on the outside of tumor cells, which allows for tumor-directed therapy that does not affect the body’s normal cells. Still other targeted therapies inhibit proteins within the tumor cell’s pathway that would normally allow for its growth, thus leading to cell death.

“Before any of these drugs are made available in pediatric patients, they must prove to be safe and effective in adults,” says pediatric oncologist Stacey Zahler, DO.

She continues, “Hopefully, as we find drugs that are more effective than what we currently use as standard of care, those drugs will be FDA-approved and made available to all patients.”

Combining chemotherapy with targeted therapies

Most clinical trials are focused on the use of targeted therapies along with chemotherapy.

Dr. Zahler thinks combining these targeted therapies along with conventional chemotherapy could be instrumental in patients whose disease is high-risk, recurrent or refractory (difficult to manage).

She points to a study on neuroblastoma, the most common solid tumor cancer in children. This research was published by the Children’s Oncology Group (COG), a National Cancer Institute supported clinical trials group for childhood and adolescent cancer research. (Cleveland Clinic is one of the 200 hospitals, universities and cancer centers worldwide that is part of this collaborative pediatric oncology group.)

“The study focused on pediatric patients with refractory or relapsed neuroblastoma,” Dr. Zahler says. “Once a patient has a recurrence of neuroblastoma, the prognosis significantly decreases.”

The trial included conventional chemotherapy in addition to the FDA-approved dinutuximab, an immunotherapy drug for high-risk patients with a dismal prognosis. Combining this immunotherapy with conventional chemotherapy led to a significant 53% response rate in these patients.

“It is through studies like these, within collaborative groups such as the COG, that some of the most effective treatments for pediatric cancer have been discovered and are now the standard of care,” Dr. Zahler says.

Promising new targeted therapies

Various studies hold promise for pediatric patients with solid tumors, including:

• Research on a new class of drugs called platelet drive growth factor receptor (PDGFR) inhibitors used in combination with a chemotherapy agent called doxorubicin. This has been FDA-approved for soft tissue sarcomas in adults and is now being studied in children in phase I and II trials at various institutions across the country, including Cleveland Clinic.
• A phase II and phase III clinical trial for pediatric patients with soft tissue sarcoma through the COG at Cleveland Clinic Children’s, which involves studying the use of a tyrosine kinase inhibitor — FDA-approved for the treatment of soft tissue sarcoma in adults — in combination with conventional chemotherapy.
• The Ewing’s Sarcoma Vigil Vaccine Trial, which is an example of personalized medicine; it involves giving a vaccine that is made from the patient’s own tumor. “Along with chemotherapy, the patient receives the vaccine to facilitate the patient’s own immune system to attack the tumor,” Dr. Zahler says.
• The ONC201 investigator-initiated clinical trial written and instituted by Peter Anderson, MD. This is a phase 2 study examining a drug called ONC201, which inhibits a protein called DRD2 that is highly expressed in solid tumors such as aggressive brain tumors, some sarcomas and paraganglioma, a rare cancer that originates in the nerve cells of the adrenal glands.
• A genetic sequencing-directed targeted therapy trial through the COG (called the Pediatric MATCH trial), studying eight different potential genetic mutations of patients’ tumors and targeting therapies against them. “The COG will screen patients’ tumors for these mutations and if they are positive, they will be eligible for the treatment portion of that clinical trial,” Dr. Zahler says.
• The phase II DFMO trial, now available at Cleveland Clinic Children’s, which inhibits the synthesis of polyamines, proteins that are highly expressed in neuroblastoma as well as other tumors. This drug has previously shown markedly improved survival in patients with high-risk neuroblastoma.

These are some of the promising ways researchers are addressing the needs of children who have cancer.