Description:
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.
Title
- Brief Title: Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma
- 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
Clinical Trial IDs
- ORG STUDY ID:
COSYMO
- NCT ID:
NCT02821507
Conditions
- Conventional Chondrosarcoma
- Myxoid Liposarcoma
- Mesenchymal Chondrosarcoma
- Dedifferentiated Chondrosarcoma
Interventions
Drug | Synonyms | Arms |
---|
sirolimus and cyclophosphamide | | sirolimus and cyclophosphamide |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
sirolimus and cyclophosphamide | Experimental | combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule | - sirolimus and cyclophosphamide
|
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide |
Time Frame: | 16 weeks |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | Using the growth modulation index (GMI) to evaluate treatment efficiency |
Time Frame: | every 8 weeks until progression (average of 1 year) |
Safety Issue: | |
Description: | GMI: Time to progression during sirolimus/cyclophosphamide treatment (TTP2) divided by time to progression before start of this treatment TTP1 |
Measure: | The overall survival after start of treatment till death |
Time Frame: | every 8 weeks until progression (average of 1 year) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Leiden University Medical Center |
Last Updated
June 9, 2021