Sunshine Project Clinical Trials & Initiatives

Phase II Study of nab-Paclitaxel in Combination with Gemcitabine for Treatment of Recurrent/Refractory Sarcoma in Teenagers and Young Adults

Principal Investigator: Jonathan Gill, MD (MD Anderson Cancer Center)

Study Synopsis: An FDA approved clinical trial focused on relapsed or refractory solid tumors in children. Solid tumors account for 60% of all childhood malignancies and unlike other childhood cancers, minimal improvement in survival has been seen in the past 20 years. These disappointing results have prompted NPCF to find new agents in the fight against this disease.

Metformin is an oral anti-diabetes medication. Recent data from research experiments and analyses of previous data suggest that Metformin has anti-cancer activity. The drugs vincristine, irinotecan and temozolomide, also known as VIT, are a combination of chemotherapies that have different ways of working and different side effects. This combination has been shown to be safe and well tolerated in children with solid tumors. This trial is evaluating the tolerability and safety of increasing doses of Metformin in combination with vincristine, irinotecan, and temozolomide in children with solid tumors.

Phase II Study of nab-Paclitaxel in Combination with Gemcitabine for Treatment of Recurrent/Refractory Sarcoma in Teenagers and Young Adults

Principal Investigator: Javier Oesterheld, MD (Carolinas Medical Center/Levine Cancer Institute)

Study Synopsis: Patients who have recurrent or progressive disease following frontline treatment for osteosarcoma or Ewing sarcoma have a dismal prognosis, with less than one-fifth of patients achieving a long-term cure. Although many adolescents and young adults with localized bone or soft tissue sarcoma can become long-term survivors, more effective therapies are needed for patients who present with metastatic disease or whose tumors recur after completing therapy.

 It is thought this combination will be more tolerable and effective than other relapsed regimen used to treat this population.  This trial will look at this combination of nab-paclitaxel and gemcitabine in its ability to prevent the formation or growth of tumors in teenagers and young adults with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas.  Markers for response to therapy are cutting edge in this trial and include blood tests to determine if the cancer is responding, computer-assisted imaging reviews to determine better ways to follow disease, and biomarkers on the tumor specimens to see if a response can be predicted.

ACTION: Adoptive Cellular Therapy following Dose-Intensified Temozolomide in Newly-diagnosed Pediatric High-grade Gliomas

Principal Investigator: Duane Mitchell, MD, Ph.D. (University of Florida)

A Phase I Trial of Dose Escalation of Metformin in Combination with Vincristine, Irinotecan, and Temozolomide in Children with Relapsed or Refractory Solid Tumors

Study Synopsis: ACTIoN is an innovative immunotherapy trial for the treatment of high-grade gliomas (HGG) in children. Pediatric brain tumors like HGG are now the leading cause of cancer-related deaths in children in the United States due to the advances in the treatment of more common hematologic malignancies. Current treatments such as surgical removal of the tumor, radiation, and chemotherapy can cure many patients with other types of brain tumors; however, the prognosis for children with high-grade gliomas (HGGs) remains poor.

It is believed that the body’s immune system protects the by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. But in most patients with high-grade gliomas (HGGs), T-cells are not stimulated enough to kill the tumor. In this trial, the patient’s tumor will be used to make a vaccine which will hopefully stimulate the T-cells to kill the tumor cells, while leaving the normal cells alone.

Phase 1 Trial of the LSD1 inhibitor sp-2577 in patients with relapsed or refractory Ewing sarcoma     

Principal Investigator: Damon Reed, MD, Moffitt Cancer Center

Study Synopsis: This trial is a targeted treatment for individuals diagnosed with refractory or recurrent Ewing sarcoma. Ewing sarcoma is an aggressive, small round blue cell tumor typically presenting as a primary bone tumor in children and young adults.

This trial will be testing SP-2577, a reversible inhibitor of LSD1, an enzyme that targets EWS/FLI1 activity; the critical pathophysiologic mechanism of Ewing sarcoma, through disruption of the function of associated proteins represents an intriguing strategy for clinical intervention. This concept has been featured in Nature News, an international science publication.

Pediatric Total Cancer Care (pedsTCC)

Principal Investigator: Damon Reed, MD (Moffitt Cancer Center)

Study Synopsis: This tissue and blood banking trial was launched in 2013 with the focus to further personalize medicine for children with cancer. PedsTCC has always aimed to be a foundation from which clinicians could answer specific questions related to their patient’s cancer through the use of molecular testing. These test results can have a significant impact on the patient’s choice of therapy. Indeed rigorous studies of rare cancer and a rare patient have launched from this foundation across institutions bringing national experts to an individual’s care.

Preclinical Study of Anti-PD-1 Antibody in Combination with 5-Azacytidine in Mouse Models of Osteosarcoma

Principal Investigators: Richard Gorlick, MD (MD Anderson Cancer Center), Michael Roth, MD (Children’s Hospital at Montefiore), David Loeb, MD, Ph.D. (Johns Hopkins University), Nicolas Llosa, MD (Johns Hopkins University), Brian Ladle, MD, PhD (Johns Hopkins University), Ian Davis, MD, Ph.D. (University of North Carolina at Chapel Hill), Patrick Thompson, MD (University of North Carolina at Chapel Hill)

Study Synopsis: This study explores the ways in which certain drugs, epigenetic modifiers, change the immune system and cancer. We plan to leverage the results of this unique, 3 institution collaboration towards the development of future Sunshine Project clinical trials such as an emerging concept for assessing the therapeutic utility of checkpoint inhibitors in combination with 5-azacitidine in patients with osteosarcoma.

Osteosarcoma outcomes have not significantly improved over the past three decades. This preclinical proposal has clear translational benefits. By defining the biology and efficacy of combined therapy with an anti-PD-1 antibody and 5-azacytidine, researchers hope to establish the basis for developing this approach into a potential Sunshine Project clinical trial for children with relapsed or refractory osteosarcoma.

Role of myeloid-derived suppressor cells (MDSC) in the development of immune tolerance after allogeneic hematopoietic cell transplantation (alloHCT).

Principal Investigator: Benjamin Oshrine, MD (Johns Hopkins All Children’s Hospital)

Study Synopsis: This trial is for children and young adults undergoing a bone marrow transplant (BMT) for treatment of leukemia or lymphoma. This research is being done to better understand the process of developing immune tolerance after blood and marrow transplantation (BMT). After BMT, the immune system of the donor gradually learns to recognize the recipient as “self” to avoid problems like graft-versus-host disease, a common complication of BMT. This is called immune tolerance. Researchers hope to determine if one specific type of immune cell, called “myeloid-derived suppressor cells” (MDSCs), are involved in this process and to determine when this cell remerges after transplant.Blood will be collected from study participants undergoing BMT to compare recipients of matched related and unrelated transplants to those receiving haploidentical bone marrow transplants (from half-matched relatives).