Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

NCT02821507 | Completed Phase 2 DMC

• 1 other identifier: COSYMO
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 7

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.

Conditions

Conventional Chondrosarcoma; Myxoid Liposarcoma; Mesenchymal Chondrosarcoma; Dedifferentiated Chondrosarcoma

Outcome Measures

Primary Outcomes (1)

• The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide

  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.

  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)

• The overall survival after start of treatment till death

  every 8 weeks until progression (average of 1 year)

Study Arms (1)

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

Drug: sirolimus and cyclophosphamide

Interventions

sirolimus and cyclophosphamide DRUG

sirolimus and cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (7)

LUMC

Leiden, 2333ZA, Netherlands

Location

Hospital de Sant Pau

Barcelona, Spain

Location

Hospital Val d'Hebron

Barcelona, Spain

Location

CIO Clara Campal

Madrid, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario y Politécnico de La Fe

Valencia, Spain

Location

Instituto Valenciano de Oncología

Valencia, Spain

Location

MeSH Terms

Conditions

Liposarcoma, Myxoid; Chondrosarcoma, Mesenchymal

Interventions

Sirolimus; Cyclophosphamide

Condition Hierarchy (Ancestors)

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Chondrosarcoma; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Hans Gelderblom, Prof

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof A.J. Gelderblom

Study Record Dates

• First Submitted: January 9, 2016
• First Posted: July 1, 2016
• Study Start: June 1, 2014
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

ES (6); NL (1)