Clinical Trial: Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2, Single Arm, Multi Center Trial Evaluating the Efficacy of the COmbination of Sirolimus and cYclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and chOndrosarcoma

Brief Summary: Chondrosarcoma and liposarcoma consists of different subtypes with a wide range of patient survival. Current treatment options consist of wide surgical resection, however for patients with a local recurrence or metastatic disease the outcome is poor. New treatment options being evaluated and mouse models show in vivo that mammilian target of rapamycin (mTOR) inhibition can prevent tumour growth. mTOR is an kinase that is present in two complexes and thereby activates multiple pathways. Aberrant mTOR signalling is known to be involved in cancer cell survival. Several clinical studies for patients with bone or soft tissue sarcoma treated with mTOR inhibitors have been conducted and they show promising results. From these studies the investigators can conclude that the combination of an mTOR inhibitor with cyclophosphamide shows promising results in chondrosarcoma. With the lack of other treatment options for unresectable and metastatic chondrosarcoma or myxoid liposarcoma the Eurosarc consortium (www.eurosarc.eu) decided to treat these patients in a standardised way according to a common protocol with the combination of sirolimus and cyclophosphamide using the growth modulation index for evaluation in the current clinical study protocol.

Detailed Summary:
Sponsor: Leiden University Medical Center

Current Primary Outcome: Using the growth modulation index to evaluate time till disease progression with combination treatment of sirolimus and cyclophosphamide [ Time Frame: 16 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Comparing pre-treatment tumor material and tumor material taken during treatment using immunohistochemistry to compare activation of the pS6, Bcl-2 and mTor pathway and DNA analysis for taqman analysis to search for hotspot mutations. [ Time Frame: 8 weeks ]
  • Register adverse events to evaluate the patient safety and tolerability of the sirolimus and cyclophosphamide combination in myxoid liposarcoma and chondrosarcoma [ Time Frame: 16 weeks ]
  • To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1 [ Time Frame: 16 weeks ]
  • The median progression free survival after start of treatment [ Time Frame: 24 weeks ]
  • The overall survival after start of treatment till death [ Time Frame: 3 months ]


Original Secondary Outcome:

  • Comparing pre-treatment tumor material and tumor material taken during treatment using immunohistochemistry and DNA analysis [ Time Frame: 8 weeks ]
  • Register adverse events to evaluate the patient safety and tolerability of the sirolimus and cyclophosphamide combination in myxoid liposarcoma and chondrosarcoma [ Time Frame: 16 weeks ]
  • To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1 [ Time Frame: 16 weeks ]
  • The median progression free survival after start of treatment [ Time Frame: 24 weeks ]
  • The overall survival after start of treatment till death [ Time Frame: 3 months ]


Information By: Leiden University Medical Center

Dates:
Date Received: January 9, 2016
Date Started: June 2014
Date Completion: June 2017
Last Updated: July 11, 2016
Last Verified: July 2016