Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

NCT ID: NCT02821507

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2021-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

sirolimus and cyclophosphamide

Intervention Type: DRUG

Interventions

sirolimus and cyclophosphamide

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

HansGelderblom

Prof A.J. Gelderblom

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hans Gelderblom, Prof

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

LUMC

Leiden, , Netherlands

Hospital de Sant Pau

Barcelona, , Spain

Hospital Val d'Hebron

Barcelona, , Spain

CIO Clara Campal

Madrid, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario y Politécnico de La Fe

Valencia, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Countries

Netherlands; Spain

Other Identifiers

COSYMO

Identifier Type: -

Identifier Source: org_study_id