Cabozantinib for Adults With Advanced Soft Tissue Sarcoma
- Cabozantinib is a cancer treatment drug that blocks the growth of new blood vessels in tumors. It can also block a chemical on tumor cells that allows the cells to grow. A similar drug, pazopanib, is used to treat types of cancer known as sarcomas. Researchers want to see if cabozantinib can be an effective treatment for types of soft tissue sarcoma that have not responded to earlier treatments.
- To test the effectiveness of cabozantinib for soft tissue sarcomas that have not responded to standard treatments.
- Individuals at least 18 years of age who have soft tissue sarcomas that have not responded to standard treatments.
- Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies and other tests will be used to study the tumor before the start of treatment.
- Participants will take cabozantinib tablets daily for 28-day cycles of treatment. The tablets should be taken whole on an empty stomach.
- Treatment will be monitored with frequent blood tests and imaging studies. - Participants will continue to take cabozantinib for as long as the tumor does not become worse and the side effects are not too severe.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Cabozantinib (XL184), a Dual Inhibitor of MET and VEGFR, in Patients With Metastatic Refractory Soft Tissue Sarcoma|
- Assess the response rate (CR+PR) of in patients with soft tissue sarcomas. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Assess the 6 month progression free survival (PFS) of cabozantinib in soft tissue sarcomas. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Determine the reduction of phospho MET in tumor biopsies post admin of XL184. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Determine and compare levels of total MET, pMET, HIF-1alpha, in biopsy samples prior/post treatment. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Determine and compare circulating level of HGF, soluble MET (sMET), VEGF-A, and soluble VEGFR2 (sVEGFR2) prior to and following administration of cabozantinib [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
- Soft tissue sarcomas (STS) are a relatively rare heterogeneous group of tumors that constitute about 1% of adult cancers.
- The mainstay of treatment for advanced disease has been palliative chemotherapy with a median overall survival of approximately 12 months. This has not changed considerably in the past years and there is an unmet need for newer targeted therapies.
- VEGF levels are elevated in patients with STS and various sarcoma cell lines express high levels of activated c-Met receptor.
- We hypothesize that dual targeting of the VEGF and c-MET pathways with cabozantinib would result in clinical benefit in patients with soft tissue sarcoma.
- Assess the response rate (CR+PR) of cabozantinib in patients with soft tissue sarcomas.
- Assess the 6 month progression free survival (PFS) of cabozantinib in soft tissue sarcomas.
-Determine and compare circulating levels of HGF, soluble MET (sMET), VEGF-A, and soluble VEGFR2 (sVEGFR2) prior to and following administration of cabozantinib.
- Patients must have had disease progression following one line of standard therapy
- Age greater than or equal to 18 years.
- Adequate organ function.
- Patients will be stratified based on prior VEGFR TKI therapy.
- All patients will receive cabozantinib at 60 mg PO daily in 4 week cycles.
- Tumor response evaluations by imaging will be done every 2 cycles.
- The study will be conducted as a dual-endpoint two-stage Phase II trial to target objective tumor response rate (CR+PR) of 30% against an unacceptably low rate of 10%, and 6-month PFS rate of 65% against an unacceptably low rate of 45% (corresponding to median PFS of 9.6 vs. 5.2 months).
- The trial will accrue up to 50 patients.
|Contact: Michelle Eugeni, R.N.||(301) email@example.com|
|Contact: Shivaani Kummar, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|