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

NCT02008019 | Suspended Phase 2 DMC

• 1 other identifier: CHONRAD
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 12

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 The treatments will be taken for 4 weeks before surgery, apart from any premature withdrawn

Conditions

Chondrosarcoma

Keywords

Chondrosarcoma; Neoadjuvant therapy; Phase II; Everolimus; Success Rate; Progression Free Survival; Overall Survival; Safety; Quality of Life; Molecular study (ancillary study)

Outcome Measures

Primary Outcomes (1)

• Success Rate obtained per arm

  A success is defined as a variation (decrease) of Ki67 expression \> 10% during treatment

  4 weeks after inclusion

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  At time of progression in the course of the 3 years follow up after randomization

• Safety

  In the course of the 3 years after randomization

• Overall Survival

  At time of death if occuring during the 3 years of follow up after randomization

• Quality of Life

  From randomization to the end of the 3 years follow up

Study Arms (3)

No treatment

NO INTERVENTION

No Everolimus treatment before surgery

Everolimus 2,5 mg/day

EXPERIMENTAL

Everolimus treatment at 2,5 mg/day for 30 days

Drug: Everolimus 2.5 mg/day

Everolimus 10 mg/day

EXPERIMENTAL

Everolimus treatment at 10 mg/day for 30 days

Drug: Everolimus 10 mg/day

Interventions

Everolimus 2.5 mg/day DRUG

Comparison between 2,5 mg/day of Everolimus per os to 10 mg/day, or to no treatment, taken during 30 days before chondrosarcoma surgery

Also known as: Afinitor; Votubia; RAD-001

Everolimus 2,5 mg/day

Everolimus 10 mg/day DRUG

Comparison between 10 mg/day of Everolimus per os to 2.5 mg/day, or to no treatment taken during 30 days before chondrosarcoma surgery

Also known as: Afinitor; Votubia; RAD-001

Everolimus 10 mg/day

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (12)

Institut Bergonié

Bordeaux, Gironde, 33076, France

Location

Institut Claudius Regaud

Toulouse, Haute Garonne, 31052, France

Location

Centre Hospitalier Universitaire de Limoges, Hôpital Dupuytren

Limoges, Haute Vienne, 87042, France

Location

Institut Régional du Cancer de Montpellier

Montpellier, Hérault, 34298, France

Location

Centre Hospitalier Régional Universitaire de Tours, Hôpital Trousseau

Tours, Indre et Loire, 37044, France

Location

Centre Hospitalier Universitaire de Nantes, Hôtel Dieu

Nantes, Loire Atlantique, 44093, France

Location

Institut de Cancérologie de l'Ouest - René Gauducheau

Saint-Herblain, Loire Atlantique, 44805, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, Meurthe et Moselle, 54511, France

Location

Centre Oscar Lambret

Lille, Nord, 59000, France

Location

CHRU de Lille - Hôpital Roger Salengro

Lille, Nord, 59037, France

Location

Centre Léon Bérard

Lyon, Rhône, 69373, France

Location

Institut Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

Related Publications (30)

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MeSH Terms

Conditions

Chondrosarcoma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jean-Yves Blay, Professor

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

• François Gouin, Professor

  Centre Hospitalier Universitaire de Nantes, Hôtel Dieu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 11, 2013
• Study Start: August 14, 2014
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2019
• Last Updated: August 7, 2017

Record last verified: 2017-08

Locations

FR (12)