- To evaluate the treatment efficiency by time to progression according to RECIST 1.1
ID
Source
Brief title
Condition
- Skeletal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to progression after start of treatment according to RECIST 1.1
Secondary outcome
- 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/cyclophosphamide treatment (TTP2)
divided by time to progression before start of this treatment TTP1 (=growth
modulation index)
Background 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 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 we 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 or metastatic chondrosarcoma or myxoid
liposarcoma the Eurosarc consortium 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.
Study objective
- To evaluate the treatment efficiency by time to progression according to
RECIST 1.1
Study design
Patients will be treated with the combination of sirolimus and
cyclophosphamide. The treatment will be given in a 4 week cycle with
cyclophosphamide in a dose of 200mg oral on day 1 to 7 and day 15 to 21.
Sirolimus will be given daily at a dose of 4mg oral. Patients will be evaluated
according to the growth modulation index on day 0 and after each second cycle.
For translational research three core biopsies are taken from the patients
maximum 21 days before the start of the treatment unless a paraffin block or 20
unstained slides from the primary tumour are available and after 7-8 weeks of
treatment.
Intervention
cyclophosphamide 200mg oral on day 1 to 7 and day 15 to 21.
Sirolimus 4mg oral daily
Study burden and risks
Patient will get one or two extra tumour biopsies with the known risks
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
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 chondrosarcoma
- 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
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
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | COSYMO |
| EudraCT | EUCTR2013-005155-32-NL |
| CCMO | NL47304.058.14 |