Sunshine Project Clinical Trials & Initiatives

S&T: Sorafenib and Topotecan

Principal Investigator: Damon Reed, MD, Moffitt Cancer Institute

Study Synopsis: Topotecan & Sorafenib in relapsed or refractory solid tumors. (Completed 5/2005), Published in “Cancer Medicine” 11/2005.

Topotecan is a chemotherapy drug that has been used safely in children with anti-cancer activity in Leukemias, solid tumors, and brain tumors.  Sorafenib is from a newer class of targeted chemotherapy drugs with safety data in children when used alone has activity in multiple pediatric research models.  The combination of these two agents was tested and found to work well together to kill cancer cells.  Thirteen patients participated at six sites.  The majority of patients were able to tolerated the combination therapy and remain at home. Three patients had to be admitted to the hospital.  The concept continues to be an attractive model.


ALL: VPLD + Metformin

Principal Investigator: Julio Barredo, MD, University of Miami Sylvester Comprehensive Cancer Center

A Phase I Window, Dose Escalating and Safety Trial of Metformin in Combination with Induction Chemotherapy in Relapsed Refractory Acute Lymphoblastic Leukemia: Metformin with Induction Chemotherapy of Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD)

Study Synopsis: An FDA approved clinical trial focused on treating relapsed acute lymphoblastic leukemia (ALL), one of the most common cancers in children. Dr.  Barredo’s  lab at the University of Miami discovered a remarkable target in ALL known as AMPK. AMPK is a central switch in cells that regulates cell growth and division. In ALL, AMPK is turned off allowing the leukemia cell to grow out of control. This makes turning AMPK back on in ALL an attractive idea for treatment.

Metformin, commonly known as GlucophageTM, is a medication frequently used to treat Type II and is also thought to possibly turn the AMPK back on. Metformin has been associated with a decreased risk for cancer incidence in diabetic patients treated with metformin versus other anti-hyperglycemics (Decensi, A., et al, 2010), therefore, the combination of metformin and chemotherapy is a possible new way to target resistant leukemia cells.

This trial will help researchers learn more about the safety and feasibility or capability of adding metformin to induction chemotherapy (the first part of a treatment) for children with ALL. Researchers will also study the maximum tolerated dose of metformin when given two times a day by mouth to children receiving induction chemotherapy and to find out how the body processes this medicine.


Solid Tumors: VIT+metformin

Principal Investigator: Jonathan Gill, MD, The Children’s Hospital at Montefiore

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: 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 PCF 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 will evaluate the tolerability and safety of increasing doses of Metformin in combination with vincristine, irinotecan and temozolomide in children with solid tumors.


Pediatric Total Cancer Care      

Principal Investigator: Damon Reed, MD, Moffitt Cancer Center

Study Synopsis: In the beginning of 2013, a new trial was launched that focused on tissue and blood collection to further personalized medicine for children with cancer. When cancer is suspected, a patient undergoes a biopsy to establish the diagnosis.  For some cancers, the therapy is entirely based on the pathologist’s interpretation of this tissue, while some cancers have molecular testing done to either confirm the diagnosis or choose a type of therapy. These test results can have a significant impact on the patient’s choice of therapy.

This trial will allow for a centralized collection of tumor tissue for molecular testing. The results may lead to a better understanding of a child’s malignancy or may lead to a better matching of therapy to the patient. Our hope is that this may guide the patient to a clinical trial from which they’d be predicted to derive the most benefit.


Gemcitabine and Nab-Paclitaxel

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

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

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 long-term cure. Although many adolescent 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.

 The FDA has approved the use of gemcitabine and nab-palatal for the treatment of advanced pancreatic cancer and it is thought this combination will be more tolerable and effective than the current regimen of gemcitabine + docetaxel 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 sarcoma.  The trial will also look at the length of time during and after treatment that the disease does not get worse, and determine.  If nab-paclitaxel combined with gemcitabine is safe and tolerable. 


Brain Tumors

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

Principal Investigator    Duane Mitchell, MD, PhD, University of Florida

Study Synopsis: An immunotherapy trial for the treatment of high grade gliomas (HGG) in children. Pediatric brain tumors 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 up to 70% of children with medulloblastoma, the most common pediatric brain tumor, the prognosis for children with high-grade gliomas (HGGs) remains abnormally 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 patients 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.


LSD1 inhibitor

Principal Investigator  Dr. Sunil Sharma

Study Synopsis: Ewing’s sarcoma is a devastating adolescent disease that today can only be treated with strong chemotherapy, radiation and surgery.  This results in about a 50% cure rate but leaves many patients who are cured with lifelong chronic diseases.  Those patients not cured by this regimen cannot be further treated with curative intent, although their lives can be prolonged with various rescue regimens.  So far, targeted therapies tried have not shown beneficial activity.   This project will be used to support research and development efforts relating a unique therapy (lysine specific histone demethylase 1 (LSD1) inhibitor) addressing Ewings Sarcoma.  Research and development efforts might include, but are not limited to pre-clinical studies (bio-availability, tolerability and toxicology), formulation efforts and other activities necessary to accelerate the initiation of clinical studies with this therapy.