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

NCT01804374 | Completed Phase 2 DMC

• 1 other identifier: SERIO
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Osteosarcoma; Relapsed Osteosarcoma

Keywords

osteosarcoma; sorafenib; everolimus; sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival rate at 6 months

  Progression Free Survival rate at 6 months refers to the rate of patients alive and free from progression of the disease at 6 months from registration into the study. Disease will be assessed every 8 weeks up to 2 years until progression or death whichever came first.

  6 months from registration into the study

Secondary Outcomes (7)

• progression free survival

  From randomization until progression or death whichever came first up to 2 years

• overall survival

  From randomization until death followed up to 5 years

• Overall response rate

  From randomization until progression or death whichever came first up to 2 years

• Duration of response

  calculated from date of first assessement of non-progression until progression or death whichever came first up to 2 years

• Non-dimensional pattern of response

  calculated from randomization until progression or death whichever came first up to 2 years

Other Outcomes (3)

• Expression of MAPKs pathway, VEGFR, PDGFR, Ezrin/Moesin and mTOR pathway (pS6 expression)

  as soon as tissue samples are available or within 2 months from subject study entry

• Correlation between oncogenes/metabolic pathways and clinical outcome parameters

  at the time of first survival analysis performed at least 6 months after last subject registration

• Predictive and prognostic role of serum lactate dehydrogenase and serum alkaline phosphatase

  at the time of first survival analysis performed at least 6 months after last subject registration

Study Arms (1)

sorafenib and everolimus

EXPERIMENTAL

This is an open label study: all patients will be treated with sorafenib 400 mg twice a day in combination with everolimus 5mg per day

Drug: Sorafenib; Drug: Everolimus

Interventions

Sorafenib DRUG

Sorafenib tablet 200 milligrams packed in bottle containing 140 tablets. Sorafenib will be administered orally twice daily at the same time every day. Two 200 mg tablets will be taken either one hour before or two hours after a meal followed by a glass of water in the morning and in the evening. In general, patient should have a low to moderate fat meal. Patients will receive Sorafenib until progression, toxicity, withdrawal of informed consent or clinical investigator decision

Also known as: BAY 43-9006, Nexavar

sorafenib and everolimus

Everolimus DRUG

Everolimus is formulated in tablets of 2.5 or 5 mg strength, blister-packed under aluminum foil in units of 10 tablets. Everolimus will be administered orally once daily at the same time every day immediately after a meal, as a single dose of 5 mg. Patients should have a low-fat breakfast. After this light meal, study medication of Everolimus is to be taken. The tablets of Everolimus should not be chewed or crushed. Patients will receive Everolimus until progression, toxicity, withdrawal of informed consent or clinical investigator decision

Also known as: RAD001, Afinitor, Certican

sorafenib and everolimus

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Italian Sarcoma Group: lead

Study Sites (1)

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, 10060, Italy

Location

Related Publications (1)

• Grignani G, Palmerini E, Ferraresi V, D'Ambrosio L, Bertulli R, Asaftei SD, Tamburini A, Pignochino Y, Sangiolo D, Marchesi E, Capozzi F, Biagini R, Gambarotti M, Fagioli F, Casali PG, Picci P, Ferrari S, Aglietta M; Italian Sarcoma Group. Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial. Lancet Oncol. 2015 Jan;16(1):98-107. doi: 10.1016/S1470-2045(14)71136-2. Epub 2014 Dec 11.

  PMID: 25498219 DERIVED

MeSH Terms

Conditions

Osteosarcoma; Sarcoma

Interventions

Sorafenib; Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Sirolimus; Macrolides; Lactones

Study Officials

• Massimo Aglietta, MD

  IRCC Candiolo

  PRINCIPAL INVESTIGATOR

• Giovanni Grignani, MD

  IRCC Candiolo

  STUDY DIRECTOR

• Piero Picci, MD

  Italian Sarcoma Group

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: March 5, 2013
• Study Start: June 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 17, 2015

Record last verified: 2015-06

Locations

IT (1)