Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

Sponsor

Leiden University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02821507

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Conventional Chondrosarcoma Myxoid Liposarcoma Mesenchymal Chondrosarcoma Dedifferentiated Chondrosarcoma	Drug: sirolimus and cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Dec 1, 2021

Actual Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sirolimus and cyclophosphamide combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule	Drug: sirolimus and cyclophosphamide

Arm

Intervention/Treatment

Experimental: sirolimus and cyclophosphamide

combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule

Drug: sirolimus and cyclophosphamide

Outcome Measures

Primary Outcome Measures

The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide [16 weeks]

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. [8 weeks]
Register adverse events to evaluate the patient safety and tolerability of the sirolimus and cyclophosphamide combination in myxoid liposarcoma and chondrosarcoma [every 8 weeks until progression (average of 1 year)]
To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1 [every 8 weeks until progression (average of 1 year)]
Using the growth modulation index (GMI) to evaluate treatment efficiency [every 8 weeks until progression (average of 1 year)]
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 [every 8 weeks until progression (average of 1 year)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	LUMC	Leiden	Netherlands	2333ZA
2	Hospital de Sant Pau	Barcelona	Spain
3	Hospital Val d'Hebron	Barcelona	Spain
4	CIO Clara Campal	Madrid	Spain
5	Hospital Universitario Virgen del Rocío	Sevilla	Spain
6	Hospital Universitario y Politécnico de La Fe	Valencia	Spain
7	Instituto Valenciano de Oncología	Valencia	Spain