The NCI is working with the Children's Oncology Group (COG) to develop a precision medicine clinical trial for children and adolescents ages 1-21 years of age with advanced cancers who have progressed on standard therapy.
The trial, known as NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice), is not yet accruing, but plans are to start enrolling patients by mid-2017. COG, which is supported through the NCI, consists of more than 200 pediatric centers in the U.S., Canada, Switzerland, Australia, New Zealand, and the Netherlands.
Adult MATCH Trial
NCI's Adult MATCH trial, which opened in August 2015, is a precision medicine clinical trial to analyze patients' cancerous tumors to determine whether they contain gene abnormalities for which a targeted drug exists (actionable mutations) and assigns a treatment matched to the abnormality.
"There are no other cancer clinical trials of this size and scope that truly bring the promise of targeted treatment to patients whose cancers have specific abnormalities," said acting NCI Director Douglas Lowy, MD, of the Adult MATCH trial. In Adult MATCH, the match rate is about 25 percent. Adults aged 18 and older with advanced solid tumors, lymphomas, and myelomas that are no longer responding (or never responded) to standard therapy and have begun to grow may be candidates for Adult MATCH, which is a very popular trial.
Differences of Pediatric MATCH
The Pediatric MATCH trial differs from NCI's Adult MATCH trial in several key ways, said Nita L. Seibel, MD, Head of NCI's Pediatric Solid Tumor Therapeutics, Clinical Investigations Branch, Cancer Therapy and Evaluation Program, Division of Cancer Treatment and Diagnosis, and Co-Chair of the Pediatric MATCH trial. "One of the main differences will be in the number of treatment arms in Pediatric MATCH as compared to Adult MATCH, and this is because of the number of targets and the types of targets," she explained. "Many of the targets for Adult MATCH are not relevant to Pediatric MATCH since we do not see those genetic aberrations in tumors in children and adolescents."
Pediatric MATCH will initially open with 6-8 treatment arms, with at least nine planned. The trial will add more arms as they are developed and their protocols approved. Seibel said it is anticipated that just 10 percent of children and adolescents will have a mutation that can be matched to a targeted drug (based on the number of mutations/genetic alterations seen in tumors from children and adolescents), as compared with the 25 percent in Adult MATCH. Adult MATCH has more than 30 treatment arms, in contrast to Pediatric MATCH.
"EGFR mutations, HER2 mutations, and amplifications occur rarely if at all in pediatric tumors, whereas these are treatment arms in Adult MATCH," noted Seibel. The number of pediatric patients screened will be much smaller: about 300 a year for a total of 1,000 patients, compared to about 125 patients a week for a total of 6,000 in Adult Match.
Seibel explained for Oncology Times how the Pediatric MATCH trial was envisioned and developed. "We had a committee (Target and Agent Prioritization Committee for Pediatric MATCH) made up of experts from the COG, NCI, and FDA to discuss what were the most common molecular targets/aberrations in tumors in children and adolescents," she said. "This list is what guided what agents we wanted to include in Pediatric MATCH." Then the committee had discussions with individual pharmaceutical companies who had agents that targeted the specific genetic abnormalities to determine the best one to include in Pediatric MATCH.
Some of the agents included in Pediatric MATCH were not included in Adult MATCH initially, Seibel noted, but have subsequently been included. For example, those designing Pediatric MATCH wanted to have a FGFR (fibroblast growth factor receptor) inhibitor, but it had to be one that covered FGFR1-4, since FGFR4 mutations are seen in pediatric tumors. In Adult MATCH, by contrast, there was an agent included that targeted FGFR1-3.
In another example of a difference between Adult MATCH and Pediatric MATCH, a different ALK inhibitor is being used in Pediatric MATCH in comparison to Adult MATCH. That, said Seibel, is because "the one used in Adult MATCH is already approved for this use, and therefore a child with an ALK mutation in their tumor most likely would have already been treated with it."
Seibel said Pediatric MATCH includes an EZH2 inhibitor and TRK inhibitor, which were not included in Adult MATCH initially. "We are using an agent that targets two pathways whereas they used a separate agent for each of the pathways," she explained, adding that Pediatric MATCH is using only single agents, whereas Adult MATCH is using a few combinations of agents.
Study Protocols
The protocol for Pediatric MATCH differs from that of ADULT MATCH. Seibel explained the pediatric patients will need to have a biopsy from the time of their cancerous tumor's progression or recurrence, but it does not have to be done immediately before they are enrolled in Pediatric MATCH. In fact, she said, the biopsy could have been done a month before or several months before enrolling in the Pediatric MATCH trial. Also, patients with diffuse intrinsic pontine gliomas and brain stem gliomas can enroll in Pediatric MATCH if they had a biopsy done at the time of diagnosis that can be submitted to be analyzed. Histiocytosis is also considered an eligible diagnosis on Pediatric MATCH.
On Adult MATCH, there is a requirement that, if a patient has been enrolled on two treatment arms, he or she has to undergo another biopsy. "This is not the case for Pediatric MATCH," noted Seibel. "There is no requirement for a biopsy if they have been enrolled on more than one arm and develop progressive disease or if they have been treated on one arm for a prolonged period of time."
Germline analysis will be part of Pediatric MATCH, but it is not a routine part of Adult MATCH. Pediatric MATCH will use the same gene platform for analysis as is used in Adult MATCH, but Seibel said that instead of having this done at four laboratories it will be done at two: the University of Texas MD Anderson Cancer Center in Houston and the Molecular Characterization & Clinical Assay Development Laboratory (MoCha Lab) at Frederick National Laboratory for Cancer Research.
Asked by Oncology Times about enrollment once Pediatric MATCH begins to accrue, Seibel stated, "When it is open for enrollment, then the treating pediatric oncologist will need to be a member of the Children's Oncology Group or refer the patient to a hospital/cancer center that is a member of the Children's Oncology Group."
Peggy Eastman is a contributing writer.