Medical Research

The intent of the Medical Research Funding is not only to support proposals that are focused on synovial sarcoma based on strong science but also to establish collaborations between scientists and physicians who are passionate about finding a cure.  Advancements in this field have been slow and the L4OF would like to accelerate breakthroughs in understanding the disease and discovering new treatment strategies. Proposals are evaluated by the Foundation Board and priority is given to research projects that are specific to synovial sarcoma and will yield the highest potential impact.

Clinical Trials

The following clinical trials are currently recruiting in age groups 0-65 for synovial sarcoma and have been active since 2016. For additional trials from earlier dates visit www.clinicaltrials.gov. We recommend you consult with your primary physician when exploring clinical trial options.

*L4OF is providing these clinical studies as an informational resource only and does not endorse or recommend any specific study.

New Approaches

Cancer research is a dynamic field with new and exciting discoveries and advances constantly happening. Below are some brief descriptions of new drugs currently being studied in different clinical trials. This list is not comprehensive and if you have further questions about these or other drugs, consult your physician.

NY-ESO-1

  • Human tumor antigen that is being studied as a possible target for immunotherapy
  • Researchers are developing genetically modified T cells (type of immune system cell) to target NY-ESO-1 which has been found to be expressed in a majority (80%) of synovial cell sarcoma tumors
  • There is a study out of the NIH that observed response in 4 out of 6 cases of synovial sarcoma[3]
  • Currently in the US, there are studies at the City of Hope (Duarte, CA), University of Miami, Moffitt Cancer Center (Tampa, FL), National Cancer Institute, Dana-Farber Cancer Institute, Washington University School of Medicine, Memorial Sloan Kettering Cancer Center, Children’s Hospital of Philadelphia, MD Anderson Cancer Center, Montefiore-Einstein Cancer Center
  • The purpose of this study is to test the good and bad effects of treatment in patients with unresectable, metastastic, or recurrent synovial sarcoma [4]

4. “A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1c259T in HLA-A2+ Patients with Synovial Sarcoma.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT01343043

TRABECTEDIN (YONDELIS)

  • Currently used in unresectable or metastatic liposarcoma or leiomyosarcoma
  • In treating synovial sarcoma, thought to inhibit (block) the biological activity of the fused protein that results from the SS18-SSX fusion gene (see “Further Workup”)
  • Study included 61 patients with metastatic synovial sarcoma treated at four different sarcoma referral centers in Europe
  • Age range of patients: 18-68 years old
  • Patients received 1-22 cycles
  • Dosages ranged from 1.1-1.5 mg/m2
  • Overall, 50% of patients achieved some form of tumor control (including partial, minor, and stable response) [5]

5. Sanfilippo, Roberta, et al. “Trabectedin in advanced synovial sarcomas: a multicenter retrospective study from four European institutions and the Italian Rare Cancer Network.” Anticancer Drugs, vol. 26, no. 6, Jul. 2015, pp. 678-681.

SELINEXOR

  • Phase I trial (focus of trial is to find the best dose of drug with fewest side effects) out of Memorial Sloan Kettering Cancer Center studying use of Selinxor in advanced refractory bone or soft tissue sarcoma
  • 4 out of the 54 patients had synovial sarcoma
  • Selinexor best tolerated at 60mg on a 3-weeks-on, 1-week-off schedule
  • Age range of patients: 18-86 years old
  • Most common side effects: nausea, vomiting, loss of appetite, fatigue
  • Other side effects: low platelet, hemoglobin, white blood cell counts
  • No patients had complete or partial responses
  • 30 of the 52 patients did have stable disease
  • 13 of 43 evaluable patients showed a reduction in target lesion size
  • Most of these patients were those with dedifferentiated liposarcoma
  • 1 of the 4 patients with synovial sarcoma had reduction in target lesion size [6]

6. Gounder, Mrinal, et al. “Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients with Advanced Refractory Bone or Soft Tissue Sarcoma.” Journal of Clinical Oncology, vol. 34, no. 26, 10 Sept. 2016, pp 3166-3174.

DHEA

  • Drug targeting a key regulatory protein for the survival of synovial sarcoma
  • Investigators are hoping to cause cell death of synovial sarcoma by blocking the production of this protein
  • Currently, there is a study out of the Washington University School of Medicine studying the maximum tolerated dose, as well as progression-free rate in utilization of this drug [7]

7. “DHEA in Synovial Sarcoma Patients.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02683148

ANLOTINIB

  • Phase 2 study out of China reported efficacy of anlotinib in various soft tissue sarcomas that progressed after anthracycline-based chemotherapy
  • 31% of patients they studied had synovial sarcoma, 15.66% of patients had leiomyosarcoma, 11.45% of patients had malignant fibrous histiocytoma
  • Dosage used: 12 mg daily on a 2 weeks on, 1 week off schedule
  • While some response was observed, those with leiomyosarcoma and alveolar soft part sarcoma seemed to benefit the most from anlotinib
  • Most common side effects: high blood pressure, elevated triglyceride levels, pneumothorax [8]
  • There is currently a phase 3 study open, called APROMISS
  • Primary aim in this study is to assess the safety and efficacy of anlotinib in treating metastatic/advanced alveolar soft part sarcoma, leiomyosarcom, and synovial sarcoma
  • Study locations: UCLA, Stanford, University of Miami, University of Michigan, Washington University St. Louis, Thomas Jefferson Hospital [9]

8. Chi, Yihebali, et al. “Phase II study of Anlotinib for Treatment of Advanced Soft Tissue Sarcomas.” ASCO. 5 June 2016.

9. “A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, and Synovial Sarcoma (APROMISS).” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT03016819

TAZEMETOSTAT (EZH2 INHIBITOR)

  • Showed encouraging clinical activity during early clinical development
  • Common side effects include fatigue, decreased appetite, nausea, and anemia
  • Currently there is a phase 2 trial open to study use of tazemetostat as a single-agent to treat relapsed/refractory synovial sarcoma [10]
  • There is also a phase 1 study for pediatric patients (6 months to 21 years old) with relapsed or refractory synovial sarcoma [11]

10. “A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects with INI1-Negative Tumors or Relapse/Refractory Synovial Sarcoma.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02601950

11. “ A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects with Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02601937

OLARATUMAB (LARTRUVO)

  • Monoclonal antibody against platelet-derived growth factor receptor alpha (PDGF-R α)
  • Often used in combination with doxorubicin
  • Common side effects include low blood counts, nausea/vomiting, fatigue, high blood sugar levels, hair loss
  • There currently is a study for patients 18 years and older with unresectable or metastatic soft tissue sarcoma to study the effects of adding Olaratumab to standard therapy
  • Researchers will be looking at how this addition affects progression of disease [12]

12. “Doxorubicin with Upfront Dexrazoxone Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02584309

Grants

The Live for Others Foundation (L4OF) Donor Advised Fund makes grants for basic and clinical research aimed at finding a cure for synovial sarcoma (SS). This disease is very rare and research into finding effective treatments and, ultimately, a cure are nascent at best. The founder of L4OF lost his battle with SS and created L4OF with the hopes of one day finding a cure for this disease. It is expected that award amounts will range between $50,000 and $100,00, however, requests for smaller or greater amounts may be considered.

Grants Awarded

Novel Mechanisms of Flavokawain A Targeting Synovial Sarcoma

Flavokawain A (FKA) represents a novel treatment strategy against synovial sarcoma (SS) by inhibiting the cellular Wnt pathway and changes in apoptosis-related pathways. Aim 1 of the research is to determine whether FKA induces anti-tumor activity in SS by inhibiting Wnt signaling and by modulating apoptosis pathway components. Aim 2 is to assess the efficacy of FKA as a pharmacologic inhibitor in an in vivo model of SS.

Apply for Grant Funding

The intent of the Medical Research funding is not only to support innovative research proposals that are focused on synovial sarcoma that are based on strong science but also to establish collaborations between scientist and physicians passionate about finding a cure for this rare and underfunded disease. Advancements in this field have been slow and the L4OF would like to accelerate breakthroughs into the basic understanding of SS as well as new treatment strategies. Proposals are evaluated by the L4OF Board and priority is given to research projects that are specific to SS and have the highest potential impact.

View Complete Application Requirements

Applications will be accepted by L4OF via email and/or mail.

The email address is research@L4OF.org.

The mailing address is:

Live for Others Foundation
C/O Orange County Community Foundation
4041 MacArthur Blvd, Ste 510
Newport Beach, CA 92660

ShareMD Patient Registry

Finding a cure for synovial sarcoma will require the generation, collection and use of medical history data from patients who are dealing with this disease. It is our goal to create a registry / database of patient information that will be made available to physicians and researchers in their efforts to find a cure. This program is a volunteer, patient and parent-led initiative and is not associated with any medical institution. If you are interested in participating in the ShareMD Patient Registry, please email us for more information.

Support L4OF in finding a cure.

X