Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

Leiden University Medical Center (LUMC)

Status and phase

Completed

Phase 2

Conditions

Mesenchymal Chondrosarcoma

Dedifferentiated Chondrosarcoma

Conventional Chondrosarcoma

Myxoid Liposarcoma

Treatments

Drug: sirolimus and cyclophosphamide

Study type

Interventional

Funder types

Other

Identifiers

NCT02821507

COSYMO

Details and patient eligibility

About

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.

Enrollment

70 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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