Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma
Primary Purpose
Conventional Chondrosarcoma, Myxoid Liposarcoma, Mesenchymal Chondrosarcoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
sirolimus and cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Conventional Chondrosarcoma
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
Sites / Locations
- LUMC
- Hospital de Sant Pau
- Hospital Val d'Hebron
- CIO Clara Campal
- Hospital Universitario Virgen del Rocío
- Hospital Universitario y Politécnico de La Fe
- Instituto Valenciano de Oncología
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
sirolimus and cyclophosphamide
Arm Description
combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule
Outcomes
Primary Outcome Measures
The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide
Secondary Outcome Measures
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.
Register adverse events to evaluate the patient safety and tolerability of the sirolimus and cyclophosphamide combination in myxoid liposarcoma and chondrosarcoma
To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1
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
The overall survival after start of treatment till death
Full Information
NCT ID
NCT02821507
First Posted
January 9, 2016
Last Updated
April 19, 2022
Sponsor
Leiden University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02821507
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
December 2021 (Actual)
Study Completion Date
December 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Conventional Chondrosarcoma, Myxoid Liposarcoma, Mesenchymal Chondrosarcoma, Dedifferentiated Chondrosarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
sirolimus and cyclophosphamide
Arm Type
Experimental
Arm Description
combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule
Intervention Type
Drug
Intervention Name(s)
sirolimus and cyclophosphamide
Primary Outcome Measure Information:
Title
The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
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
Title
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)
Title
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)
Title
Using the growth modulation index (GMI) to evaluate treatment efficiency
Description
GMI: Time to progression during sirolimus/cyclophosphamide treatment (TTP2) divided by time to progression before start of this treatment TTP1
Time Frame
every 8 weeks until progression (average of 1 year)
Title
The overall survival after start of treatment till death
Time Frame
every 8 weeks until progression (average of 1 year)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Gelderblom, Prof
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
LUMC
City
Leiden
ZIP/Postal Code
2333ZA
Country
Netherlands
Facility Name
Hospital de Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Val d'Hebron
City
Barcelona
Country
Spain
Facility Name
CIO Clara Campal
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
Country
Spain
Facility Name
Hospital Universitario y Politécnico de La Fe
City
Valencia
Country
Spain
Facility Name
Instituto Valenciano de Oncología
City
Valencia
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma
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