NCI-COG Pediatric MATCH trial to test targeted drugs in childhood cancers

Today investigators at the National Cancer Institute (NCI) and the Children’s Oncology Group (COG) announced the opening of enrollment for a unique precision medicine clinical trial. NCI-COG Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH) is a nationwide trial to explore whether targeted therapies can be effective for children and adolescents with solid tumors that harbor specific genetic mutations and have progressed during or after standard therapy. Pediatric MATCH will incorporate more than eight different study drugs, each targeting a predefined set of genetic mutations, to match patients with therapies aimed at the molecular abnormalities in their tumors.

The study was developed and will be led jointly by NCI, part of the National Institutes of Health, and COG, part of the NCI-sponsored National Clinical Trials Network.

Pediatric MATCH is a phase 2 trial with sub-studies (arms) for each targeted drug being investigated. It will open with approximately six treatment arms, expanding to eight or more. A similar trial for adults, NCI-MATCH, began enrolling adult patients in August 2015 and is also matching patients to treatments based on the genetic mutations in their tumors. Pediatric MATCH is a separate trial for children and adolescents ages 1 to 21 who have solid tumors—including non-Hodgkin lymphomas, brain tumors, and histiocytoses—that no longer respond to standard treatment or have recurred after treatment.

“Pediatric MATCH is a very special trial,” said Douglas R. Lowy, M.D., NCI acting director. “There aren’t any other cancer trials of this scale exploring targeted treatments for children whose cancers have specific genetic abnormalities. Precision medicine trials like Pediatric MATCH have the potential to accelerate progress in identifying more effective treatments for children with cancer.”

The trial has two enrollment steps. Each patient will initially enroll for a screening study, in which a sample of his or her relapsed tumor will undergo DNA and RNA sequencing to detect genetic abnormalities that could be targeted by one or more of the drugs being studied. Archived tumor samples can be used if they were obtained after the tumor progressed following initial treatment. If there is a genetic abnormality identified in the tumor and a drug in Pediatric MATCH that targets that abnormality, the patient can then enroll in the corresponding treatment arm if he or she meets the eligibility criteria.

Pediatric MATCH will use a single sequencing test to screen for many molecular abnormalities at once. The test, which is also being used for the adult NCI-MATCH trial, was developed by the Molecular Characterization Laboratory at the NCI-sponsored Frederick National Laboratory for Cancer Research (FNLCR) in Frederick, Maryland. The latest version of this test looks for alterations in more than 160 genes associated with cancer.

To ensure quality control, biopsy specimens from all patients will be sent to a single location, the COG Biopathology Center at Nationwide Children’s Hospital in Columbus, Ohio, for DNA and RNA processing. The sequencing analysis for Pediatric MATCH will be done at two laboratories that carried out sequencing for adult NCI-MATCH: the FNLCR and MD Anderson Cancer Center.

Cancer mutations that match one of the drugs being studied are expected to be found in only about 10 percent of tumors from children and adolescents with cancer. The trial investigators, therefore, project that they will screen 200 to 300 patients a year, for a total of 1,000 patients screened, to identify patients potentially eligible for each of the sub-studies. Patients with a matched drug will be able to receive treatment as long as their tumors remain stable in size or get smaller. At least 20 patients will be targeted for enrollment in each arm, and additional treatment arms will be added as the trial progresses.

“Pediatric MATCH is a cutting-edge trial in many ways,” said COG chair Peter C. Adamson, M.D., of the Children’s Hospital of Philadelphia. “It will bring molecular analysis, coupled to a portfolio of new targeted agents, to children and adolescents with relapsed cancer across the United States. Importantly, it will also help us learn more about relapsed cancer in pediatric patients, catalyzing research aimed at developing better treatments.”

The drugs being used in Pediatric MATCH are all investigational (experimental) agents in children and contributed by pharmaceutical companies that have partnered with NCI to support this study.

“This trial would not have been possible without the enthusiastic support of the partnering pharmaceutical companies, as evidenced by their willingness to provide targeted agents for this trial,” said NCI study co-chair Nita Seibel, M.D., of NCI’s Division of Cancer Treatment and Diagnosis. “Some of the agents included have not previously been tested in children, so this trial will provide broader access to targeted agents for children and adolescents.”

Although most of the DNA mutations identified in study patients will be present only in cancer cells and not elsewhere in the body, some may have been inherited. For this reason, in Pediatric MATCH “we will also look at whether mutations found in tumors are detected in blood samples and hence were inherited,” said COG study co-chair Will Parsons, M.D., Ph.D., of Baylor College of Medicine in Houston. “This will allow us to provide the treating physician with guidance for the patient’s family regarding the need for formal genetic testing, counseling, and follow-up care.”

Patients found not to have a matched drug may, with the help of their oncologists, be able to enroll in other studies available through the COG Developmental Therapeutics Program, Pediatric Brain Tumor Consortium, New Approaches to Neuroblastoma Therapy consortium, and pharmaceutical trials located through trials.cancer.gov.

Enrollment in Pediatric MATCH will be available at children’s hospitals, university medical centers, and cancer centers across the United States that are part of COG. Sites will access the trial under the protocol identification APEC1621 via the NCI Cancer Trials Support Unit.

Additional Resources: For more information on NCI-Pediatric MATCH, go to www.cancer.gov/nci-pediatricmatch.

About the National Cancer Institute (NCI): NCI leads the National Cancer Program and the NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI's Contact Center (formerly known as the Cancer Information Service) at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov.

About the Children’s Oncology Group (COG): COG, a member of NCI’s National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites more than 9,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, New Zealand, and parts of Europe in the fight against childhood cancer. Today, more than 90 percent of the 14,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. COG’s mission is to improve the cure rate and outcome for all children with cancer. For more information, visit childrensoncologygroup.org.