A Phase II Study of EVEROLIMUS in Patients With Primary or Relapsed Chondrosarcomas

• Status: Suspended
• Trial end date: 2019-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The mainstay of chondrosarcoma treatment is a wide surgical resection. Unfortunately, this is a rare occurrence, and patients with incomplete resection have very poor therapeutic options. In this context, it becomes important to find new therapeutic strategies to slow down tumor progression and to reduce tumor size before resection.

Pre-clinical and clinical data suggest that EVEROLIMUS should be efficient as adjuvant and neo-adjuvant therapy in chondrosarcoma.

Then, investigators propose a phase II, randomized, open label study compounded by 3 arms (1:1:1) to assess efficiency of EVEROLIMUS as neo-adjuvant therapy in patients with primary or relapsed chondrosarcomas :

ARM 1 = No treatment; ARM 2 = 2,5 mg Everolimus/day; ARM 3 = 10 mg Everolimus/day.

The treatments will be taken for 4 weeks before surgery, apart from any premature withdrawn

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Leon Berard
• Treatments: Everolimus; Sirolimus

Criteria

INCLUSION CRITERIA :

• Male or Female ≥ 18 years

• Histopathologically confirmed diagnosis of primary or relapsed conventional CHS of the bone (with or without metastases), CHS of any size on MRI if relapse OR size ≥ 10 cm on MRI at diagnosis OR CHS < 10 cm if R0 resection with adequate margins is not feasible at 1st examination (localization, tumor infiltration within surrounding tissues).

• Patient with life expectancy > 6 months

• Planned surgery between D32- D40 after inclusion

• Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2

• No contra-indication to Everolimus as per Summary of Product Characteristics (SPC)

• Adequate bone marrow, liver and renal functions including the following:

• Hemoglobin > 9 g/dL

• Neutrophil count ≥ 1500 x 109/L

• Platelets ≥ 100 x 109/L

• Total bilirubin ≤ 1,5x upper limit of normal (ULN)

• Serum Glutamate Oxaloacetate Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) ≤ 3 x ULN

• Alkaline Phosphatase ≤ 2,5 x ULN

• Serum creatinine < 110 µmol/L or creatinine clearance > 55 ml/min (estimated by Cockcroft Formula)

• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.

• Ability to understand and willingness to sign a written informed consent

• In accordance with French Regulatory Authorities: Patients with French Social Security in compliance with the French law relating to biomedical research (Huriet Law 88-1128 and related decrees)

• Women of child-bearing potential and men must agree to use adequate double contraception prior to study entry, for the duration of study participation and 30 days after the last study drug intake.

EXCLUSION CRITERIA :

• Mesenchymal, dedifferentiated, clear cell subtype chondrosarcoma, and soft tissues chondrosarcoma

• Tumor tissue sample not available for pathological review/or correlative studies

• Patients may not be receiving any other investigational agents

• Prior treatment with mTOR inhibitors

• Symptomatic congestive heart failure of New York heart Association Class III or IV

• Uncontrolled diabetes as defined by fasting serum glucose >160 mg/dl or 8.9 mmol/l

• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease

• Chemotherapy within the last 4 weeks before inclusion; radiotherapy, or any other investigational agent within 14 days or 5 half-lives, whichever is longer prior to the first dose of study drug

• Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study

• Impaired cardiac function or clinically significant cardiac diseases, or liver, respiratory or hepatic disease

• Known diagnosis of HIV infection

• Patient with ongoing toxicity Grade ≥ 2 according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0

• Pregnant or breast feeding women (a pregnancy test will be performed within 7 days before inclusion).