Skip to main content
OpenTrials
Completed

NCT Number: NCT02821507

Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Conventional Chondrosarcoma Chondrosarcoma Chondrosarcoma, Mesenchymal Dedifferentiated Chondrosarcoma Liposarcoma Liposarcoma, Myxoid Mesenchymal Chondrosarcoma Myxoid Liposarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Adipose Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Sarcoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

LUMC, Leiden, Netherlands

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

sirolimus and cyclophosphamide

Drug

Primary outcomes

  1. The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide

    Time frame: 16 weeks

Secondary outcomes

  1. 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

  2. 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)

  3. 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)

  4. 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

  5. The overall survival after start of treatment till death

    Time frame: every 8 weeks until progression (average of 1 year)

Sponsors and collaborators

Lead sponsor

Leiden University Medical Center

Other

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2021
Study completion
2021
First posted
Jul 1, 2016
Registry last updated
Apr 20, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.