Project Update (December 2019)

With support from the ALSF Center of Excellence grant, Dr. Steven Dubois at the Dana-Farber Cancer Institute led a clinical trial for larotrectinib, a drug for treating pediatric cancers with the NTRK fusion gene. The clinical trial led to the FDA approval of larotrectinib in December 2018. Read more on the ALSF blog.

In the clinical trial led by Dr. Dubois, over 75-percent of patients treated responded positively and their tumors either shrunk or disappeared. One of those patients, 6-year-old Lakelynn, is battling an inoperable sarcoma wrapped around the nerves that control her right arm. Lakelynn joined the trial in 2016. Her tumor shrunk and remains stable.

“All of us have seen patients lose their struggle with cancer and that's not okay. The status quo is not acceptable," said Dr. Dubois

Project Update (July 2019)

This research has resulted in a clinical trial at Dana Farber Cancer Institute in Boston, Massachusetts. The phase 1 clinical trial called, Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitor BMS-986158 in Pediatric Cancer is studying an investigational drug called BMS-986158 as a possible treatment for pediatric solid tumors, lymphoma, or brain tumors. The study is open to all pediatric patients with relapsed solid tumors; but investigators are particularly interested in patients with MYC- or MYCN-driven tumors such as medulloblastoma and neuroblastoma.

Full details of the trial.

Dana-Farber Cancer Institute/Boston Children's Hospital (DFCI-BCH) has a plan to create a Developmental Therapeutics Unit for pediatric cancer that integrates a scientific agenda, teamwork and resources for effective conduct of pediatric cancer clinical trials, unsurpassed patient care by cancer specialists, and education of young doctors who will become leaders. Our ultimate goal is curative therapy for children with cancer; infrastructure and well-trained clinical investigators are necessary to achieve this goal. As more personalized therapies are tested and utilized in our program, a Developmental Therapeutics Unit is of key importance. With this funding, we move ideas from our exceptional laboratory-based research programs into the clinic to treat patients, focusing on targeted anti-cancer drug development and cell therapies. We will commit to the training of three clinician/researchers in the field of developmental therapies: teaching expertise in drug development and application of innovative therapies.

Funding from Alex's Lemonade Stand Foundation will sustain our relatively new infrastructure, and support four primary new initiatives:

1. To create a Developmental Therapeutics Unit, including creation of a new position, the Developmental Therapeutics Clinical Research Manager;
2. To provide patients with increased access to clinical trials of novel agents, and provide treating physicians with increased awareness of existing/open clinical trials of novel agents at DFCI-BCH;
3. To facilitate collaboration among the sites of ALSF COEs, and increase the number of innovative phase I and II clinical trials for rare pediatric cancers; and,
4. To build a Pediatric Oncology Developmental Therapeutics Training Program at DFCI-BCH.

Project Update (March 2018)

Congratulations to ALSF Center of Excellence Grantee Dr. Steven DuBois from Dana-Farber Cancer Institute for his February 22, 2018 published article in the New England Journal of Medicine. The article, “Efficay of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children,” concluded that Larotrectnib, had marked durable anti tumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or of the tumor type. A total of 55 patients, ranging in age from 4 months to 76 years, were enrolled and treated with Larotrectnib, with an overall response rate of 75-percent. Read full-article.

Project Update (September 2014)

Wendy B. London, PhD and Carlos Rodriguez-Galindo, MD answered questions about the ALSF-funded Center of Excellence project.

Why did you choose to create a Center of Excellence at Boston Children’s Dana-Farber Cancer and Blood Disorders Center?
We saw this as an opportunity to improve our infrastructure for the conduct of innovative clinical trials, especially in regards to junior faculty members who may not have sufficient grant funding for infrastructure to support their trials.

How long does it take to study a new therapeutic intervention?
It can take as long as 15 years to bring a new compound/treatment from discovery and testing in the laboratory to licensure by the FDA. For treating children with cancer, sometimes we test combinations of drugs that have been already licensed for treatment of adults with cancer. However, children often need a different approach than adults, and it is critical that we continue our search for efficacious new drugs for children.

How many studies do you run for concurrently for childhood cancer?
At Boston Children’s Dana-Farber Cancer and Blood Disorders Center, we are actively participating in over 100 oncology studies at any given time, about 50 of which are therapeutic trials.

What obstacles/challenges do you face in bringing new treatments to children with cancer?
Lack of sufficient funding is the biggest obstacle. From a scientific perspective, we are actively moving to the use of targeted therapies. We have the ability to profile the DNA of the child’s cancer and identify genetic aberrations. Our challenge is that we frequently do not know the meaning/role of these genetic aberrations, and we often do not have a treatment that matches that aberration. However, investigators at Boston Children’s Dana-Farber Cancer and Blood Disorders Center are taking the lead in developing a new study to systematically profile the solid tumors of children with cancer, and attempt to match their genetic aberrations to available drugs.

What has this grant from ALSF allowed you to do that you wouldn’t be able to do otherwise?
Support the Scholars – give them protected time to conduct their innovative research. We have been able to hire more staff, which means that we can open more trials and studies.

What are Developmental Therapeutic Scholars? How are the scholars being trained and what is the long term expectation for them?
The developmental therapeutics scholars are junior researchers who are working on developing new treatments for children with cancer. We have two categories of Developmental Therapeutic Scholars: an Experimental Therapeutics Scholar, who is working on the development of new chemotherapeutic agents, and a Cell Therapeutics Scholar, who is developing new cell therapies. Both Scholars receive very comprehensive training in clinical and laboratory research methods, with the goal of developing an independent academic career in developmental therapeutics for children with cancer.

Have you achieved effectiveness for any of the therapeutics you are studying?
The Boston Children’s Dana-Farber Cancer and Blood Disorders Center has actively participated in trials that have shown effectiveness for the following new treatments:

• ch14.18 antibody – 15% improvement in the overall survival rate post-transplant
• ALK inhibitor – early indication of activity within neuroblastoma patients who have an ALK mutation
• ALSF Scholar Andrew Place, MD has recently activated a Phase I trial of KPT-330 in pediatric patients with relapsed/refractory acute leukemia. This trial is open at all four ALSF COE sites, plus three additional hospitals. Once an appropriate dose (MTD) has been determined, the efficacy of this therapy can be studied.
• ALSF Scholar Susanne Baumeister, MD will be testing a therapy utilizing an NKG2D-CAR molecule; the clinical trial protocol is currently undergoing scientific review. A protocol to test the GVAX vaccine in patients with neuroblastoma will be submitted for IRB review within the next few weeks.

What does this mean for children with cancer and their families?
The impact that the development of new therapies has in children with cancer and their families is immense. It is only through this type of initiatives and training of new investigators that we will advance towards to goal of curing all children with cancer. Also, it is very important for children with cancer and their families to feel part of the fight and participate of clinical trials and the research experience.