Patients with high-grade Osteosarcoma, not resectable/metastatic, failing at least 2 different lines of standard tr4eatment for relapsed/metastatic disease MedDRA version: 14.1 Level: PT Classification code 10031294 Term: Osteosarcoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 5-
Sponsors
ITALIAN SARCOMA GROUP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically documented and not surgically resectable or metastatic high-grade osteosarcoma which progressed after first or second line treatments for relapsing disease. 2. Measurable disease as defined by having at least one uni-dimensional (RECIST v1.1 / bone lesions are allowed) measurable lesion that can be accurately measured by means of CT or MRI. Baseline evaluations must be completed within 28 days prior to enrollment. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0/ 1 and an estimated life expectancy of at least 3 months. Patients with an ECOG PS 2 are eligible if the PS 2 depends solely on orthopedic problems. 4. Estimated life expectancy of at least 3 months. 5. age =18 years. 6. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of treatment: - Hemoglobin > 9.0 g/dl - Absolute neutrophil count (ANC) >1,500/mm3 - Platelet count ? 100,000/µl - Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. 2. Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. In particular for history of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. 3. History of HIV infection and active clinically serious infections (> grade 2 NCI-CTC version 4.03). 4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry). 5. Patients with seizure disorders requiring medication (such as steroids or anti-epileptics). 6. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 8 weeks after last dose of study drug. 7. Patients with evidence or history of bleeding diathesis. 8. Patients undergoing renal dialysis. 9. Patients unable to swallow oral medications. 10. Uncontrolled diabetes (fasting glucose > 2 x ULN). 11. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone = 20 mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for = 4 weeks prior to the first dose of RAD001. Topical or inhaled corticosteroids are permitted. 12. Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer skin or other solid tumors curatively treated with no evidence of disease for =3 years. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs). 13. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. 14. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study. 15. Investigational drug therapy outside of this trial during or within 4 weeks of study entry. 16. Prior exposure to the study drugs or their analogues. 17. Patients with known hypersensitivity to sorafenib, RAD001 or other rapamycin analogs (sirolimus, temsirolimus), or to its excipients. 18. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results. 19. A history of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of the study will be to assess the antitumor activity of sorafenib 400 mg twice a day in combination with everolimus 5mg/die as second or third line treatment of relapsed unresectable/metastatic high-grade osteosarcoma;Secondary Objective: Secondary objectives of the study will be to explore the activity of the combination sorafenib and everolimus in this unfavorable Osteosarcoma subset. This will be accomplished by both recording overall survival, progression-free survival, duration of response, RECIST response rate (dimensional reduction), non-dimensional response rate (metabolic or functional responses), safety and oncogene activation and correlation with outcomes parameters. Any improvement in patients’ quality of life will be captured by the Pain and Analgesic scale and recorded as clinical benefit. Finally, a specific effort will be conducted to evaluate the pattern of response, if any, given the peculiar patterns of response observed in solid tumors with molecular-targeted therapy.;Primary end point(s): Progression Free Survival at 6 months;Timepoint(s) of evaluation of this end point: Disease status will be assessed every 2 months interval by TC/MR depending on disease site/s. Patients free from progression of the disease (RECIST 1.1) at 6 month assessment will be considered as success. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS), Progression-free survival (PFS), Overall response rate (ORR), Duration of response, Non-dimensional pattern of response (i.e. metabolic or functional), Clincal benefit, Safety (according to CTC version 4.03);Timepoint(s) of evaluation of this end point: October 2013 | — |
Countries
Italy
Contacts
Public ContactD.O. Oncologia Medica a Dir.Univ.
Fondazione del Piemonte per l'Oncologia IRCC Candiolo
Outcome results
None listed