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Phase II Open Label, Non-randomized Study of Sorafenib and Everolimus in Relapsed and Non-resectable Osteosarcoma

Information source: Italian Sarcoma Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Metastatic Osteosarcoma; Relapsed Osteosarcoma

Intervention: Sorafenib (Drug); Everolimus (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Italian Sarcoma Group

Official(s) and/or principal investigator(s):
Massimo Aglietta, MD, Principal Investigator, Affiliation: IRCC Candiolo
Giovanni Grignani, MD, Study Director, Affiliation: IRCC Candiolo
Piero Picci, MD, Study Chair, Affiliation: Italian Sarcoma Group

Summary

This is a trial for patients affected by metastatic or relapsed osteosarcoma which progressed after first or further line treatments. In this trial, all patients will be treated until progression or unacceptable toxicity with sorafenib and everolimus. The treatment with sorafenib and everolimus aimed to obtain a 50% rate of patients free from further progression of the disease after 6 months from study entry.

Clinical Details

Official title: A Phase II, Open Label, Non-randomized Study of Second or Third Line Treatment With the Combination of Sorafenib and Everolimus in Patients Affected by Relapsed and Non-resectable High-grade Osteosarcoma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Progression Free Survival rate at 6 months

Secondary outcome:

progression free survival

overall survival

Overall response rate

Duration of response

Non-dimensional pattern of response

clinical benefit

Safety

Detailed description: Patients affected by metastatic or relapsed osteosarcoma which progressed after first or further line treatments still have a poor outcome. Standard chemotherapy has limited activity in these patients. In a previous study in patient affected by relapsed unresectable osteosarcoma, sorafenib alone demonstrated promising activity. In the preclinical setting, everolimus was able to improve the activity of sorafenib. Sorafenib and everolimus, by hitting crucial pathways which are essential for osteosarcoma cell proliferation and survival, with an entirely different approach aimed to overcome the resistance to standard chemotherapy showed by relapsed osteosarcoma. In this trial, all patients will be treated with sorafenib and everolimus at the dosage of 800 mg and 5 mg per day, respectively. Both drugs have to be taken orally. The treatment will be continued until progression or unacceptable toxicities. The objective of the present trial is to obtain a 50% rate of patients alive and free from progression of their disease 6 months after trial enrolment. The disease will be evaluated every 2 months with a CT scan.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients with histologically documented and not surgically resectable or metastatic

high-grade osteosarcoma which progressed after first or second line treatments for relapsing disease

- Measurable disease as defined by RECIST criteria vs. 1. 1 (bone lesions are allowed).

Baseline evaluations must be completed within 28 days prior to enrollment

- Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1. ECOG PS 2

patients are eligible if the PS 2 depends solely on orthopedic problems

- Estimated life expectancy of at least 3months

- Age≥18 years

- Adequate bone marrow, liver and renal function: Hemoglobin>9. 0g/dl, Absolute

neutrophil count>1,500/mm3, Platelet>100,000/μl Total bilirubin<1. 5 times the upper limit of normal (ULN), ALT and AST<2. 5xULN (<5xULN for patients with liver involvement of their cancer), PT-INR/PTT<1. 5xULN, Serum creatinine<2xULN

- Written informed consent

Exclusion Criteria:

- Dementia or significantly altered mental status that would prohibit the understanding

or rendering of informed consent and compliance with the requirements of this protocol

- Patients with any severe and/or uncontrolled medical conditions such as unstable

angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function.

- History of HIV infection and active clinically serious infections (>grade 2 according

to NCI-CTCAE vs. 4. 0)

- Symptomatic metastatic brain or meningeal tumors (unless the patient is >6months from

definitive therapy, has a negative imaging study within 4weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)

- Patients with seizure disorders requiring medication

- Pregnant or breast-feeding patients. Women of childbearing potential must have a

negative pregnancy test performed within 7days of the start of treatment. Both men and women must use adequate barrier birth control measures during the course of the trial and 8weeks after last dose of study drug

- Patients with evidence or history of bleeding diathesis

- Patients undergoing renal dialysis

- Patients unable to swallow oral medications

- Uncontrolled diabetes (fasting glucose>2xULN)

- Patients receiving chronic, systemic treatment with corticosteroids or another

immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤20mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for ≥4weeks prior to the first dose of Everolimus. Topical or inhaled corticosteroids are permitted

- Patients with a history of another malignancy within 5years 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 ≥3years. 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

- Anticancer chemotherapy or immunotherapy during the study or within 4weeks of study

entry

- Radiotherapy during study or within 3weeks of start of study drug. (Palliative

radiotherapy will be allowed)

- Major surgery within 4weeks of start of study

- Investigational drug therapy outside of this trial during or within 4weeks of study

entry

- Prior exposure to the study drugs or their analogues

- Patients with known hypersensitivity to sorafenib, everolimus or other rapamycin

analogs, or to its excipients

- Substance abuse, medical, psychological or social conditions that may interfere with

the patient's participation in the study or evaluation of the study results

- A history of noncompliance to medical regimens or inability or unwillingness to

return for scheduled visits

Locations and Contacts

Fondazione del Piemonte per l'Oncologia IRCC Candiolo, Candiolo, Torino 10060, Italy
Additional Information

Starting date: June 2011
Last updated: June 16, 2015

Page last updated: August 23, 2015

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