AzTrials
AzTrials

Metastatic OsteosarcomaPhase 2SERIONCT01804374

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

A Phase 2 study testing Sorafenib and Everolimus in people with Metastatic Osteosarcoma and Relapsed Osteosarcoma, run by Italian Sarcoma Group at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sorafenib and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteItaly
Study dates
Jun 2011to Dec 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Fondazione del Piemonte per l'Oncologia IRCC Candiolo

    Candiolo, Torino, 10060

Other trials in Italy

About this study

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

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.

Read the 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.

Being tested
Sorafenib, Everolimus
Keywords
osteosarcoma, sorafenib, everolimus, sarcoma
Medical subject headings
Osteosarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SorafenibDrug

    Also called BAY 43-9006, Nexavar

    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

  • EverolimusDrug

    Also called RAD001, Afinitor, Certican

    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

Study groups in NCT01804374
Study groupRoleWhat they receive
sorafenib and everolimusExperimentalThis is an open label study: all patients will be treated with sorafenib 400 mg twice a day in combination with everolimus 5mg per day
Receives: Drug: Sorafenib; Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months from registration into the study

Secondary outcomes (7)

  1. progression free survival

    Progression Free Survival (PFS) refers to the time from registration into the study to the date of progressive disease or death whichever came first assessed every 8 weeks up to 2 years. In the absence of progression, time will be censored at the date of last tumor assessment or follow-up

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

  2. overall survival

    Overall survival (OS) is the time interval between date of registration into study and the date of death. For alive patients, time will be censored at the date of last follow-up.

    Measured: From randomization until death followed up to 5 years

  3. Overall response rate

    Overall response rate refers to the rate of patients with complete, partial or minimal responses (defined as shrinkage of target lesions between 10 and 30%) according to RECIST 1.1. Disease will be assessed every 8 weeks up to 2 years.

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

  4. Duration of response

    Duration of response refers to the time from the date of the first assessement of non-progression to the date of progressive disease or death. Disease will be assessed every 8 weeks up to 2 years until progression or death whichever came first. In the absence of progression time will be censored at the date of last tumor assessment or follow-up.

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

  5. Non-dimensional pattern of response

    Non-dimensional pattern of response refers to the evaluation of any consistent variation in radio metabolic diagnostic test (i.e. PET or Bone scan) and/or changes in signal intensity, contrast uptake/enhancement and tumor density at CT/MRI according to Modified Response Criteria (MRC). From this point of view, patients will be considered in response if there has been an objective response or at least ONE of the following criteria are met:

    1. An unequivocal reduction in tumor density at CT scan;
    2. An unequivocal reduction in signal intensity and/or contrast enhancement at MRI;
    3. An unequivocal reduction in SUV at PET scan;
    4. An unequivocal reduction in bone scan uptake.

    Disease will be assessed every 8 weeks up to 2 years until progression or death whichever came first.

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

  6. clinical benefit

    Clinical Benefit will be prospectively evaluated by means of Pain and Analgesic Scale recording of analgesic consume and as lack of progression of disease at six months.

    Measured: evaluated at each visit from randomizzation until progression or death whichever came first up to 2 years

  7. Safety

    Safety will be captured by recording: physical examinations, vital signs, performance status/body weight; blood tests and chemistry tests; intensity and severity of adverse events, use of analgesic medication at each visit until 28 days after last dose of study treatment assumption up to 2 years. Adverse events will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    Measured: assessed at each visit from randomizzation until 28 days after the last dose of study treatment assumption up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Mar 2013 (estimated)
  2. Study startJun 2011
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01804374
Sponsor's protocol ID
SERIO
Acronym
SERIO
Status last verified
Jun 2015
First submitted
1 Mar 2013
Last updated
17 Jun 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25498219

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sorafenib and Everolimus in people with Metastatic Osteosarcoma and Relapsed Osteosarcoma, run by Italian Sarcoma Group at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival rate at 6 months (time frame: 6 months from registration into the study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01804374, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2015.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in