Conventional ChondrosarcomaPhase 2NCT02821507
Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma
A Phase 2 study testing sirolimus and cyclophosphamide in people with Conventional Chondrosarcoma and Myxoid Liposarcoma, run by Leiden University Medical Center at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Conventional Chondrosarcoma, Myxoid Liposarcoma, Mesenchymal Chondrosarcoma
- What is being tested?
- sirolimus and cyclophosphamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jun 2014to Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Spain6 sites
Hospital de Sant Pau
Barcelona
Hospital Val d'Hebron
Barcelona
CIO Clara Campal
Madrid
Hospital Universitario Virgen del Rocío
Seville
Hospital Universitario y Politécnico de La Fe
Valencia
Instituto Valenciano de Oncología
Valencia
About this study
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
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.
- Conditions
- Conventional Chondrosarcoma, Myxoid Liposarcoma, Mesenchymal Chondrosarcoma, Dedifferentiated Chondrosarcoma
- Being tested
- sirolimus and cyclophosphamide
- Medical subject headings
- Liposarcoma, Myxoid, Chondrosarcoma, Mesenchymal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimus and cyclophosphamideDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: sirolimus and cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide
Measured: 16 weeks
Secondary outcomes (5)
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.
Measured: 8 weeks
Register adverse events to evaluate the patient safety and tolerability of the sirolimus and cyclophosphamide combination in myxoid liposarcoma and chondrosarcoma
Measured: every 8 weeks until progression (average of 1 year)
To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1
Measured: every 8 weeks until progression (average of 1 year)
Using the growth modulation index (GMI) to evaluate treatment efficiency
GMI: Time to progression during sirolimus/cyclophosphamide treatment (TTP2) divided by time to progression before start of this treatment TTP1
Measured: every 8 weeks until progression (average of 1 year)
The overall survival after start of treatment till death
Measured: every 8 weeks until progression (average of 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2016 (estimated)
- Study startJun 2014
- Primary completionDec 2021
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Conventional ChondrosarcomaStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, HansGelderblom, Leiden University Medical Center
- Investigators
- Hans Gelderblom, Prof, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02821507
- Sponsor's protocol ID
- COSYMO
- Status last verified
- Apr 2022
- First submitted
- 9 Jan 2016
- Last updated
- 20 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02821507
- Acronym / sponsor ID
- COSYMO
- Conditions
- Conventional Chondrosarcoma, Myxoid Liposarcoma, Mesenchymal Chondrosarcoma, Dedifferentiated Chondrosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Dec 2021 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 1 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sirolimus and cyclophosphamide | Experimental | Drug: sirolimus and cyclophosphamidecombining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimus and cyclophosphamide | Drug | sirolimus and cyclophosphamide |
Primary outcome
The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide
Time frame: 16 weeks
5 secondary outcomes
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
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)
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)
Using the growth modulation index (GMI) to evaluate treatment efficiency
Time frame: every 8 weeks until progression (average of 1 year)
The overall survival after start of treatment till death
Time frame: every 8 weeks until progression (average of 1 year)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Gelderblom, Prof principal investigator
Leiden University Medical Center
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sirolimus and cyclophosphamide in people with Conventional Chondrosarcoma and Myxoid Liposarcoma, run by Leiden University Medical Center at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2022.