Forging Collaboration Between Children’s and Adult Oncology Groups in Designing Trials for Adolescents and Young Adults

A Conversation With Aaron R. Weiss, DO

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Brandon Hayes-Lattin, MD, FACP

Brandon Hayes-Lattin, MD, FACP

Guest Editor

Adolescent and Young Adult Oncology explores the unique physical, psychosocial, social, emotional, sexual, and financial challenges adolescents and young adults with cancer face. The column is guest edited by Brandon Hayes-Lattin, MD, FACP, Associate Professor of Medicine and Medical Director of the Adolescent and Young Adult Oncology Program at the Knight Cancer Institute at Oregon Health and Science University in Portland, Oregon.

Nonrhabdomyosarcoma soft-tissue sarcomas account for about 5% of all childhood malignancies and are also diagnosed in adolescents and young adults, as well as in older adults, and can require different approaches to treatment based on a patient’s age and stage of disease. These sarcomas comprise a diverse group of subtypes, including fibrosarcoma, leiomyosarcoma, liposarcoma, neurofibrosarcoma, peripheral nerve sheath tumors, and synovial sarcoma, and are not well studied in the pediatric or adolescent and young adult patient population.

In 2011, Aaron R. Weiss, DO, Assistant Clinical Professor of Pediatrics in the Division of Pediatric Hematology-Oncology at the Maine Medical Center in Portland, and his colleagues designed a clinical trial through the Children’s Oncology Group (COG) to evaluate adding pazopanib (Votrient) to the standard of care in nonrhabdomyosarcoma soft-tissue sarcomas, including surgery and radiation, with or without chemotherapy, to determine whether it improved survival.

This type of clinical trial collaboration has never been done before. Our hope is that it will foster similar collaboration among the oncology groups to design studies in other cancers that affect patients of every age.
— Aaron R. Weiss, DO

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Dr. Weiss then submitted the trial design to the Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute (NCI) for approval and funding. He learned that a similar protocol concept had been submitted by NRG Oncology, an adult oncology research organization consisting of the National Surgical Adjuvant Breast and Bowel Project; the Radiation Therapy Oncology Group; and the Gynecologic Oncology Group, for approval. CTEP suggested the two groups work together to develop one treatment protocol for children, adolescents and young adults, and older adults. The result is the launch of a phase II/III clinical trial known as COG-NRG ARST 1321,1 the first collaborative study co-written and conducted by both a pediatric and adult cancer consortium group.

The ASCO Post talked with Dr. Weiss about the benefits of partnering with different cooperative groups to launch studies in patients of differing ages with the same cancer.

Novel Type of Clinical Trial

Why is it important for different oncology groups to come together to study specific cancers occurring in children, adolescents and young adults, and older adults?

Having this type of buy-in from both the COG and NRG Oncology in the study of such a rare cancer like nonrhabdomyosarcoma soft-tissue sarcoma is important because the disease occurs in all age groups and incorporates numerous subtypes, which some oncologists treat individually and others lump together and treat similarly. Designing a study that takes all this information into account will, hopefully, help us learn how to treat the various subtypes of nonrhabdomyosarcoma, better understand the similarities and differences among pediatric and adult tumor biology, and personalize treatment for patients in every age group.

This type of clinical trial collaboration has never been done before. Our hope is that it will foster similar collaboration among the oncology groups to design studies in other cancers that affect patients of every age.

Preliminary Study Findings

The study launched in 2014. Do you have any preliminary results you can share?

We are still in the process of actively recruiting patients and are at the beginning stages of analyzing data, so it’s too early to provide any conclusive results. What I can say is that so far, the treatment regimen with the addition of pazopanib seems to be well tolerated.

What makes this study unique is that there are some types of nonrhabdomyosarcoma soft-tissue sarcomas that are thought to be more chemosensitive than other subtypes, so we divided this trial into two groups: a chemotherapy group and a nonchemotherapy group.

The chemotherapy group of patients receives standard chemotherapy based on tumor type, plus radiation therapy, and is randomized either to receive or not receive pazopanib. The second group is prescribed radiation therapy, plus or minus pazopanib, which is a novel concept. Most clinical studies for this cancer treat all patients with nonrhabdomyosarcoma soft-tissue sarcoma uniformly, but we are starting to recognize that may not be the best way to design trials, because the same standard-of-care approach may not be appropriate for every patient.

Treating Desmoid Tumors With Sirolimus

You have also launched a study evaluating the use of an mTOR (mammalian target of rapamycin) inhibitor, sirolimus, in the treatment of desmoid tumor in children, adolescents, and young adults. Please talk about the design of that clinical trial.

This is a smaller study than the ARST 1321 study, but because desmoid tumors are most commonly diagnosed in people between the ages of 10 and 40—although they can also be found in very young children and older adults—the design concept of recruiting both pediatric and young adult patients is the same.

Desmoid tumors are extremely rare and constitute just 0.03% of all cancers, so there is not a lot known about their natural history, and we don’t have effective therapies to treat the disease. We have a theory that the deregulation of the mTOR cell proliferation/survival pathway, which is involved in many cancers, may be involved in the tumor biology of desmoid tumors. In this study, we are evaluating whether we can block the mTOR pathway with sirolimus to potentially decrease the risk of disease recurrence in high-risk patients.

We are giving sirolimus to patients before they have surgery to remove their tumor. Then we are analyzing the tumor to see if we’ve blocked the mTOR pathway and studying the rate of recurrence in patients receiving the drug. This is a very small pilot study, but our hope is that if the mTOR pathway is indeed involved in desmoid tumors and sirolimus shows some potential benefit, we would open up the study to enroll more patients and use the therapy over a longer period, as there are so few therapeutic options beyond surgery for these patients and the disease can be devastating for those affected by it.

Launching Collaborative Group Studies

What will be the long-term result of the COG and adult cooperative groups collaborating to co-develop clinical trials to study cancers in adolescents and young adults?

Even though the NCI established the National Clinical Trials Network [NCTN] as a resource for the launch of cancer clinical trials nationally and in Canada, the reality is that within COG, we are usually aware of only the clinical studies activated in our group. So, the idea of two cooperative groups, COG and NRG Oncology, working together is a way to push the issue of making adult and pediatric providers more aware of each other’s studies and increase the potential to enroll more patients. I also think that if you can involve these cooperative groups to work together at the early design stages of a trial, they will be much more invested in the study because they will have had a say in its development.

The cooperative group process to enroll adolescents and young adults in clinical trials used to be challenging if the group involved was outside your own cooperative group. Now, the NCTN format has made it much easier to launch a collaborative group study, because the process has been so streamlined, and providers with patients across the age spectrum can open clinical trials much more quickly.

For information on the COG-NRG ARST 1321 trial in nonrhabdomyosarcoma soft-tissue sarcomas and to enroll patients, go to To learn more about the pilot study evaluating the use of the mTOR inhibitor sirolimus in children and young adults with desmoid-type fibromatosis, visit ■

Disclosure: Dr. Weiss reported no potential conflicts of interest.


1. Weiss A: COG-NRG ARST 1321: Pazopanib neoadjuvant trial in non-rhabdomyosarcoma soft tissue sarcomas (PAZNTIS): A phase II/III randomized trial of preoperative chemoradiation or preoperative radiation plus or minus pazopanib (NSC# 737754; IND#118613). Available at Accessed October 19, 2016.