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Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

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ClinicalTrials.gov Identifier: NCT02821507
Recruitment Status : Recruiting
First Posted : July 1, 2016
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
HansGelderblom, Leiden University Medical Center

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
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 : June 2014
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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Primary Outcome Measures :
  1. The time to progression after start of treatment combination treatment of sirolimus and cyclophosphamide [ Time Frame: 16 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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) ]
  3. 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) ]
  4. Using the growth modulation index (GMI) to evaluate treatment efficiency [ Time Frame: 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

  5. The overall survival after start of treatment till death [ Time Frame: every 8 weeks until progression (average of 1 year) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02821507


Contacts
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Contact: Hans Gelderblom, Prof a.j.gelderblom@lumc.nl

Locations
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Netherlands
LUMC Recruiting
Leiden, Netherlands, 2333ZA
Contact: Hans Gelderblom, Prof       a.j.gelderblom@lumc.nl   
Spain
Hospital de Sant Pau Recruiting
Barcelona, Spain
Contact: A López Pousa         
Hospital Val d'Hebron Recruiting
Barcelona, Spain
Contact: C Valverde         
CIO Clara Campal Recruiting
Madrid, Spain
Contact: J Rodriguez         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain
Contact: J Martin Broto         
Hospital Universitario y Politécnico de La Fe Recruiting
Valencia, Spain
Contact: R Diaz-Beveridge         
Instituto Valenciano de Oncología Recruiting
Valencia, Spain
Contact: J Lavernia         
Sponsors and Collaborators
Leiden University Medical Center
Investigators
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Principal Investigator: Hans Gelderblom, Prof Leiden University Medical Center
More Information
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Responsible Party: HansGelderblom, Prof A.J. Gelderblom, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT02821507     History of Changes
Other Study ID Numbers: COSYMO
First Posted: July 1, 2016    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
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Liposarcoma
Chondrosarcoma
Liposarcoma, Myxoid
Chondrosarcoma, Mesenchymal
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Connective Tissue
Sirolimus
Cyclophosphamide
Everolimus
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents