Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

Myxoid Liposarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02821507
• Other study ID #: COSYMO
• Status: Completed
• Phase: Phase 2
• Start date: June 2014
• Est. completion date: December 2021

Study information

• Verified date: April 2022
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chondrosarcoma
• Conventional Chondrosarcoma
• Dedifferentiated Chondrosarcoma
• Liposarcoma
• Liposarcoma, Myxoid
• Mesenchymal Chondrosarcoma
• Myxoid Liposarcoma

Intervention

Drug:
• sirolimus and cyclophosphamide

Locations

Country	Name	City	State
Netherlands	LUMC	Leiden
Spain	Hospital de Sant Pau	Barcelona
Spain	Hospital Val d'Hebron	Barcelona
Spain	CIO Clara Campal	Madrid
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario y Politécnico de La Fe	Valencia
Spain	Instituto Valenciano de Oncología	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Countries where clinical trial is conducted

Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide		16 weeks
Secondary	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
Secondary	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)
Secondary	To evaluate the response according to response evaluation criteria in solid tumors (RECIST) 1.1		every 8 weeks until progression (average of 1 year)
Secondary	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	every 8 weeks until progression (average of 1 year)
Secondary	The overall survival after start of treatment till death		every 8 weeks until progression (average of 1 year)