Lee J Helman, MD, Senior Investigator, Pediatric Oncology Branch, Head Molecular Oncology Section, National Cancer Institute in Bethesda, Maryland is the Principal Investigator for this clinical trial for patients with recurrent osteosarcoma which is open to accrual at sites across the United States.
Su Young Kim, MD, PhD, Assistant Clinical Investigator, Pediatric Oncology Branch, Molecular Oncology Section, National Cancer Institute in Bethesda, Maryland is the protocol chair person for this clinical trial.
Trial Background
Osteosarcoma is the most common malignant bone tumor in the United States. Unfortunately, as with any type of cancer, there is a chance of recurrence after a patient has completed therapy. Furthermore, there is currently no reliable, effective treatment for recurrent osteosarcoma. The existing standard of care is to resect the recurrent tumor if possible, followed by observation. Knowing this, the importance of identifying new biological agents and therapies for the treatment of recurrent osteosarcoma cannot be overstated.
Studies demonstrate that 95% of patients with osteosarcoma have activation of Src (a protein tyrosine kinase), or one of its substrates. Specifically, data reveals Src activation plays a role in the tumor progression of osteosarcoma. Additionally, increased activity or expression of Src has been seen in many common solid tumors, including the lung and several gastrointestinal tumors involving the esophagus, stomach, liver, pancreas and colon. Src seems to play an important role in the progression of these types of tumors as well.
AZD0530 is an experimental drug that is a potent and selective Src kinase inhibitor. Previously conducted clinical trials have shown that some adult patients with cancer who received AZD0530 had slowing of growth of their tumor. These features make AZD0530 a very attractive biological agent to move forward in advanced clinical trials. This SARC trial will be conducted to determine whether AZD0530 will be effective for patients with osteosarcoma.
Trial
The purpose of this study is to determine how long patients who undergo complete surgical removal of recurrent osteosarcoma in the lung will remain free of cancer after taking AZD0530 compared to patients taking placebo.
More specifically, this treatment protocol is a research study aimed to:
- Determine if the addition of AZD0530 can decrease the chance a tumor will come back
- Determine if the addition of AZD0530 results in an increase in survival
- To evaluate how much Src was present in the tumor sample
- Test tumor samples to see if a characteristic pattern of genes can be identified that might help researchers understand why osteosarcoma comes back
- Attempt to grow the tumor in the laboratory in order to study why it grows and how we can stop it from growing
This will be a multi-institutional, randomized, placebo-controlled, blinded trial. Therefore, after complete surgical removal of osteosarcoma recurrent in the lung, patients will be randomly assigned to receive either AZD0530 or placebo throughout the study. Neither the patient, nor the trial investigators, will know if the patient is receiving AZD0530 or placebo.
Participation in the Trial
*Patients who are eligible for this study must:
· Have histological diagnosis of recurrent osteosarcoma, localized to the lungs, had complete surgical removal of all lung nodules, or are deemed fully resectable.
· Have recurrence specifically in the lung following standard therapy including: adriamycin, cisplatin, ifosphamide and methotrexate (or justify why these agents were not given)
· Be between 15 and 74 years of age.
· Weigh over 34 kg or 74.8 lbs.
· Be at minimum ambulatory and capable of all selfcare, but may be unable to carry out any work activities, and be up and about more than 50% of waking hours.
· Demonstrate adequate bone marrow, renal, hepatic, and cardiac function.
· Sign informed consent indicating awareness of the investigational nature and the risks of this study.
*Patients must not:
· Be pregnant or nursing/breast-feeding and must be willing to use an acceptable method of contraception during participation in the study and for 3 months after the last dose.
· Have presence of metastatic disease in other locations in addition to the lung.
· Have received chemotherapy, biological or investigational agent less than 28 days prior to enrollment or be experiencing unresolved toxicity side effects from previous agents.
· Be hypersensitive to other Src/Abl non-receptor kinase inhibitors.
· Have evidence of interstitial lung disease (defined as bilateral, diffuse, parenchymal lung disease) or have disruption of the lung pleura by tumor.
· Have any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
· Have had a heart attack within one year.
*this represents only a partial list of requirements to be included or excluded from the study. A complete list is available from SARC.
For more information contact SARC at 734.930.7600 or Dr. Kim at 301-451-7018.
This trial is registered at clinicaltrials.gov and can be found at:
http://clinicaltrials.gov/ct2/show/NCT00752206?term=SARC012&rank=1
The full title is: A Randomized, Double-Blinded, Placebo-Controlled, Multi-Institutional, Phase II.5 Study of AZD0530, a Selective Src Kinase Inhibitor, in Patients with Recurrent Osteosarcoma Localized to the Lung
Glossary
*Osteosarcoma also called osteogenic sarcoma, is the most frequently occurring type of primary bone cancer. It is characterized by the production of osteoid or immature bone by malignant cells. It is seen in people of all ages, but primarily affects children and young adults, with a median age of 20 years. Osteosarcomas are found most often in the bones around the knee (femur or tibia), and usually in the growth plates at the ends of the bone (metaphysis) where there is a large amount of active bone growth.
*Placebo is an inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
*Src is a non-receptor tyrosine kinase. Activation of Src involves dual mechanism, both directly and indirectly, affecting several signaling pathways. Some of these include the PI3K/AKT/mTOR, Ras/Raf/MEK/MAPK and STAT3 pathways, all of which affect proliferation and survival of the cell. Src also targets another set of substrates at focal adhesions including focal adhesion kinase (FAK) and paxillin. The latter is a scaffolding molecule that plays an important role in cell motility and migration.