Spotlight on Clinical Trials: A Phase II Study Matches Cancer Treatments to Pediatric Patients’ Tumor Genetics
A national screening and multi–sub-study phase II trial open at DFCI is leveraging knowledge of the potential genetic causes of cancer and the latest advances in genetic analysis to match various anti-cancer drugs, each targeting a defined set of gene mutations, to different patients based on the molecular abnormalities in their individual tumors. Two DFCI faculty members are leading treatment arms of the trial, which is a cooperative effort between the National Cancer Institute (NCI) and the Children’s Oncology Group (COG).
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) is enrolling children and young adults aged 1 to 21 years who have solid tumors, including brain tumors, as well as non-Hodgkin lymphomas and histiocytoses, that no longer respond to standard treatment or have recurred after treatment.
Like a similar but separate trial for adults, investigators are using a single sequencing test to screen patients’ tumor samples for numerous genetic abnormalities. When the team identifies an alteration that is targeted by a drug being tested in Pediatric MATCH, the patient can receive the treatment if he or she meets the eligibility criteria. The trial currently has seven treatment arms open, each testing a different drug, with another two arms expected to be added as the trial progresses. The drugs being tested have shown some antitumor activity against adult tumors with particular genetic alterations. Using a strategy based on precision medicine, clinicians will treat patients based on genetic changes in their tumor, not by the type of cancer or its location in the body.
“In the past decade, precision cancer medicine has transformed the treatment of cancer for some diagnoses resulting in improved cure rates and fewer side effects from treatment; however, many children with solid cancers, lymphoma, or histiocytoses have not benefited from precision oncology,” said Katherine Janeway, MD, MMSc (DFCI), a principal investigator for one of the treatment arms and National Vice Chair of the Screening protocol. “The NCI-COG Pediatric MATCH trial brings tumor profiling and molecularly targeted therapies, the two essential components of precision cancer medicine, to children with cancer at almost 200 sites nationwide. This will allow us to better understand how to bring the benefits of precision oncology to children with these cancers in the future.”
Dr. Janeway and her colleagues hope to gather valuable information concerning the proportion of pediatric patients whose tumors have genetic alterations that can be targeted by select drugs, as well as the proportion of tumors that shrink after treatment. The team also plans to sequence the blood of each patient in addition to their tumor samples, with the goal of determining if any of the mutations are inherited and might therefore have implications for testing and cancer prevention in family members. Because patients whose tumors are not matched to a drug in the trial may be eligible to enroll in other clinical trials, results from the screening will be shared with patients’ oncologists.
The trial’s results will be helpful as new targeted therapies for cancer are developed and tested. “Through the NCI-COG Pediatric MATCH trial and other precision medicine efforts, we will gain a deeper understanding of which molecular targets are most common in childhood cancers. As a result, in the future, clinical trials of molecularly targeted drugs will simultaneously include children and adults,” said Dr. Janeway.
Based on tumor sample analyses, patients who have a molecular variant addressed by treatments included in the trial will be matched to one of the treatment arms. The goal is to enroll at least 20 patients nationwide on each treatment arm. The trial began enrolling patients in July 2017, and investigators at all sites expect to screen 200-300 patients/year for up to a total of 1,000 patients screened. The match rate of those patients screened is expected to be approximately 5-10 percent. The primary endpoint of the trial is objective response rate (complete response and partial response).
Phase II Trial
Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders
DF/HCC Principal Investigator: Katherine Janeway, MD, MMSc (DFCI)
NIH Trial Number: NCT03155620
DF/HCC Protocol Number: 17-729
The trial is recruiting patients. Find more information at ClinicalTrials.gov.
-Tracy Hampton, PhD
The Children’s Oncology Group (www.childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research with over 9,000 experts worldwide working in over 200 COG member institutions.