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Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

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ClinicalTrials.gov Identifier: NCT02821507
Recruitment Status : Recruiting
First Posted : July 1, 2016
Last Update Posted : February 25, 2020
Sponsor:
Information provided by (Responsible Party):
HansGelderblom, Leiden University Medical Center

Tracking Information
First Submitted Date  ICMJE January 9, 2016
First Posted Date  ICMJE July 1, 2016
Last Update Posted Date February 25, 2020
Study Start Date  ICMJE June 2014
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide [ Time Frame: 16 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 30, 2016)
Using the growth modulation index to evaluate time till disease progression with combination treatment of sirolimus and cyclophosphamide [ Time Frame: 16 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
  • 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: every 8 weeks until progression (average of 1 year) ]
  • To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1 [ Time Frame: every 8 weeks until progression (average of 1 year) ]
  • Using the growth modulation index (GMI) to evaluate treatment efficiency [ Time Frame: every 8 weeks until progression (average of 1 year) ]
    GMI: Time to progression during sirolimus/cyclophosphamide treatment (TTP2) divided by time to progression before start of this treatment TTP1
  • The overall survival after start of treatment till death [ Time Frame: every 8 weeks until progression (average of 1 year) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2016)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Conventional Chondrosarcoma
  • Myxoid Liposarcoma
  • Mesenchymal Chondrosarcoma
  • Dedifferentiated Chondrosarcoma
Intervention  ICMJE Drug: sirolimus and cyclophosphamide
Study Arms  ICMJE Experimental: sirolimus and cyclophosphamide
combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule
Intervention: Drug: sirolimus and cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 30, 2016)
105
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically proven conventional chondrosarcoma
  • Or pathologically proven myxoid liposarcoma with PIK3CA mutation or Phosphatase and tensin homolog (PTEN) loss
  • Or pathologically proven mesenchymal or dedifferentiated chondrosarcoma
  • Patient is 18 years and up
  • Documented radiographic progression of disease according to RECIST 1.1 criteria in last 6 months
  • Written signed informed consent
  • Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 80 x 109/L)
  • Availability of archival tumor material for central review or be able to perform a 3 core fresh biopsy
  • Ability to adhere to the study visits and all protocol requirements

Exclusion Criteria:

  • Previously treated with an mTOR inhibitor
  • Known to be allergic to cyclophosphamide
  • Life expectancy of less than 3 months
  • No measurable lesions according to RECIST 1.1
  • Eastern cooperative oncology group (ECOG) Performance status >2
  • Major surgery less than 4 weeks prior to start of treatment
  • Known human immunodeficiency virus (HIV) positivity
  • A decreased renal function with calculated glomerular filtration rate (GFR) < 30ml/min
  • Systemic anti-cancer therapy within 28 days prior to the first dose of study drug , or radiotherapy to a target lesion within 21 days prior to the first dose of study drug
  • Pregnant or lactating women
  • Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localised cured prostate and cervical cancer
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hans Gelderblom, Prof a.j.gelderblom@lumc.nl
Listed Location Countries  ICMJE Netherlands,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02821507
Other Study ID Numbers  ICMJE COSYMO
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party HansGelderblom, Leiden University Medical Center
Study Sponsor  ICMJE Leiden University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hans Gelderblom, Prof Leiden University Medical Center
PRS Account Leiden University Medical Center
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP