Conventional chondrosarcoma Myxoid liposarcoma with PIK3CA mutation or PTEN loss Mesenchymal or dedifferentiated chondrosarcoma Clear cell chondrosarcoma
Conditions
Interventions
Trade Name: Rapamune
Product Name: Sirolimus
Pharmaceutical Form: Coated tablet
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Pathologically proven conventional chondrosarcoma - Or pathologically proven myxoid liposarcoma with PIK3CA mutation or PTEN loss - Or pathologically proven mesenchymal or dedifferentiated chondrosarcoma - Or pathologically proven clear cell chondrosardoma - Patients of 18 years and up - Documented radiographic progression of disease according to RECIST 1.1 criteria in last 6 months - 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 - Written signed informed consent - Ability to adhere to the study visits and all protocol requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 93 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
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 - 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 GFR < 30 ml/min - Systemic anti-cancer therapy within 28 days prior to the first dose of study drug , or radiotherapy to an index (or 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate treatment efficacy by time to progression according to RECIST 1.1;Secondary Objective: - To evaluate the safety and tolerability of the sirolimus and cyclophosphamide combination - To determine the median progression free survival after start of treatment till disease progression - To determine the overall survival after start of treatment till death - To evaluate the treatment efficiency by growth modulation index;Primary end point(s): Time to progression after start of treatment according to RECIST 1.1;Timepoint(s) of evaluation of this end point: Patients will be evaluated with CT-scan every 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Translational exploratory tumour pharmacodynamic analysis - Toxicity according to CTC version 4.0 - Objective response defined as a partial or complete response occurring after start of treatment according to RECIST1.1 - Overall survival from start of treatment until death - Time to progression during sirolimus/cyclofosfamide treatment (TTP2) divided by time to progression before start of this treatment TTP1 (=growth modulation index);Timepoint(s) of evaluation of this end point: 1. every 4 weeks on outpartient clinic visit 2. every 8 weeks with CT-scan | — |
Countries
Netherlands, Spain
Contacts
Public ContactResearch secretary
Leiden University Medical Center
Outcome results
None listed