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• Conditions: advanced solid tumor with bone metastasis and advanced pretreated osteosarcoma.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000196-85-FR
• Lead Sponsor: Institut Bergonié

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-07
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Histology:
- Advanced solid tumor with radiologically proven bone metastasis, all tumor types (dose escalation part)
- Patients with osteogenic osteosarcoma (dose escalation part and expansion cohort) histologically confirmed by central review (Pr. Coindre team), except if the diagnosis was already confirmed by the RRePS Network,
2. Metastatic or unresectable locally advanced disease,
3. Age > 18 years for patients with solid tumor and = 13 years for patients with osteosarcoma,
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1,
5. Life expectancy > 3 months,
6. Measurable disease according to RECIST v1.1. At least one site of disease must be uni-dimensionally = 10 mm,
7. Previous use of > 1 conventional agent(s), and for patients with osteosarcoma previous use of conventional agents including anthracyclines, platinum salts, ifosfamide and/or methotrexate (neoadjuvant/adjuvant setting included),
8. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
9. Adequate haematological, renal, metabolic and hepatic function:
a. Haemoglobin = 10 g/dl (patients may have received prior red blood cell [RBC] transfusion, if clinically indicated); leucocytes = 3 x 109/l, absolute neutrophil count (ANC) = 1.5 x 109/l, and platelet count = 120 x 109/l.
b. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =2.5 x upper limit of normality (ULN)
c. Total bilirubin = 1.5 x ULN
d. Calculated creatinine clearance (CrCl) > 40 ml/min/1.73 m2 (according to MDRD formula)
e. Creatine phosphokinase (CPK) =2.5 x ULN
f. Albumin > 25 g/l
10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
11. Recovery to grade = 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade = 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4),
12. Patients with a French social security in compliance with the French law relating to biomedical research (Article L.1121-11 of French Public Health Code).
13. Voluntarily signed and dated written informed consent prior to any study specific procedure,
14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier.

Are the trial subjects under 18? yes
Number of subjects for this age range: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion Criteria

1. Previous treatment with sirolimus,
2. Concomitant diseases/conditions:
? Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural
effusions
? Unstable cardiac disease, pulse oximetry saturation < 90% at rest
? Clinically significant immunodeficiency, such as HIV or active Hepatitis B or C
? History of auto-immune disease, transplantation
3. Central nervous system malignancy (CNS),
4. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding,
5. Patients receiving any substances that are inhibitors or inducers of CYP450 3A4 (non-exhaustive list on Appendix 3),
6. Ongoing or recent (<6 weeks) dental problem, including any severe tooth or jaw infection (mandible and maxilla), dental trauma, dental or stomatological surgery (implants). Current dental cares are allowed.
7. History of maxillary osteonecrosis or delayed healing after dental surgery,
8. Participation to a study involving a medical or therapeutic intervention in the last 30 days,
9. Previous enrolment in the present study,
10. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
11. Known hypersensitivity to any involved study drug or any of its formulation components,
12. Patients receiving live vaccines within 30 days prior to the first dose of study therapy and while participating in study (Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1, rabies, BCG, and typhoid vaccine. However, if seasonally indicated, it is advised to give seasonal flu vaccine as recommended, > 15 days before C1J1.).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified