Metastatic Ewing SarcomaPhase 2NCT02243605
Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma
A Phase 2 study testing Cabozantinib S-malate and Laboratory Biomarker Analysis in people with Metastatic Ewing Sarcoma and Metastatic Osteosarcoma, run by National Cancer Institute (NCI) at 11 sites in France.
Trial summary
This phase II trial studies how well cabozantinib s-malate works in treating patients with osteosarcoma or Ewing sarcoma that has grown or returned (come back) after a period of improvement. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Metastatic Ewing Sarcoma, Metastatic Osteosarcoma, Recurrent Ewing Sarcoma
- What is being tested?
- Cabozantinib S-malate and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 11 sitesFrance
- Study dates
- 19 Dec 2014to 23 Jul 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Young patient age between 12 - 15 could be included in only 6 centers (Bordeaux, Lyon, Villejuif, Lille, Marseille and Paris)
- Patients must have histologically confirmed diagnosis of osteosarcoma or Ewing sarcoma by central review, except if the diagnosis was already confirmed by the RRePS (Reseau de Reference en Pathologie des Sarcomes et des Tissus Mous et des Visceres) network
- Relapsed disease after standard chemotherapy
- Patients must have measurable disease (lesion in previously irradiated field could be considered as measurable if progressive at inclusion) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with spiral computed tomography (CT) scan
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Life expectancy of greater than 3 months
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- Absolute neutrophil count >= 1,500/mcL
- Lymphocyte count > 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal
- Creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (Cockcroft formula)
- Hemoglobin >= 9 g/dL
- Serum albumin >= 2.8 g/dL
- Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
- Urine protein/creatinine ratio (UPCR) =< 1
- Serum phosphorus >= lower limit of normal (LLN)
- Serum calcium >= LLN
- Serum magnesium >= LLN
- Serum potassium >= LLN
- Female subjects of childbearing potential must not be pregnant at screening; females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy); however, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons
- The effects of Cabozantinib on the developing human fetus are unknown; for this reason and because tyrosine kinase inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (see below) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of cabozantinib administration
- Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)
- Metastatic or unresectable locally advanced
- Documented disease progression (as per RECIST v1.1) before study entry; for patients with osteosarcoma, this progression will be confirmed by central review on the basis of two CT scan or magnetic resonance imaging (MRI) obtained at less than 6 months in the period of 12 months prior to inclusion
- Ability to understand and the willingness to sign a written informed consent document
- In accordance with French Regulatory Authorities: Patients with French Social Security in compliance with the French law relating to biomedical research (Huriet Law 88-1138 and related decrees)
Who cannot join
- The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
- Prior treatment with cabozantinib
- Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment; systemic treatment with radionuclides within 6 weeks before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment; note: subjects with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
- The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
- The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
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- The subject has a primary brain tumor
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before the first dose of study treatment; eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
- The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
- The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
- The subject requires chronic concomitant treatment of strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)
- it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- The subject has experienced any of the following:
- Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
- Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
- Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
- The subject has radiographic evidence of cavitating pulmonary lesion(s)
- The subject has tumor in contact with, invading or encasing any major blood vessels
- The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- Cardiovascular disorders including:
- Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
- Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
- Any history of congenital long QT syndrome
- Any of the following within 6 months before the first dose of study treatment:
- Unstable angina pectoris
- Clinically-significant cardiac arrhythmias
- Stroke (including transient ischemic attack [TIA], or other ischemic event)
- Myocardial infarction
- Thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
- Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
- Any of the following within 28 days before the first dose of study treatment
- Intra-abdominal tumor/metastases invading GI mucosa
- Any evidence of active peptic ulcer disease, patients must be completely recovered
- Any evidence of inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, patients must be completely recovered from these conditions
- Malabsorption syndrome
- Any of the following within 6 months before the first dose of study treatment:
- Abdominal fistula
- Gastrointestinal perforation
- Bowel obstruction or gastric outlet obstruction
- Intra-abdominal abscess; note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment
- Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
- Other clinically significant disorders such as:
- Active infection requiring systemic treatment within 28 days before the first dose of study treatment
- Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
- History of organ transplant
- Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
- History of major surgery as follows:
- Major surgery within 12 weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment
- Minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible
- The subject is unable to swallow tablets
- The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before treatment; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
- The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
- The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib
- Pregnant women are excluded from this study because cabozantinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, breastfeeding should be discontinued if the mother is treated with cabozantinib; these potential risks may also apply to other agents used in this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cabozantinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Participation to a study involving a medical or therapeutic intervention in the last 30 days
- Prior participation in this study
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
France11 sites
Institut Bergonie Cancer Center
Bordeaux, 33076
Centre Georges-Francois Leclerc
Dijon, 21079
Centre Oscar Lambert
Lille, 59020
Centre Leon Berard
Lyon, 69373
Hopital De La Timone
Marseille, 13385
Centre Antoine Lacassagne
Nice, 06189
Institut Curie Paris
Paris, 75005
Institut de Cancerologie de l'Ouest-Rene Gauducheau
Saint-Herblain, 44805
CHRU Strasbourg - Hospital Civil
Strasbourg, 67091
Center Claudius Regaud
Toulouse, 31052
Gustave Roussy
Villejuif, 94805
About this study
Official title: A Phase 2 Study of XL184 (Cabozantinib) in Treating Patients With Relapsed Osteosarcomas and Ewing Sarcomas
This phase II trial studies how well cabozantinib s-malate works in treating patients with osteosarcoma or Ewing sarcoma that has grown or returned (come back) after a period of improvement. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may also prevent the growth of new blood vessels that tumors need to grow.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the antitumor activity of cabozantinib s-malate (cabozantinib) for Ewing sarcomas, in terms of 6-month objectives response as per the Response Evaluation Criteria in Solid Tumors, Revised (RECIST version [v]1.1).
II. To evaluate the antitumor activity of cabozantinib for osteosarcoma, in terms of 6-month objective response (complete response, partial response) and 6-month non-progression (complete response, partial response and stable disease), as per RECIST v1.1.
SECONDARY OBJECTIVES:
- 6-month objective response. (Ewing sarcoma only) II. Best overall response (as per the revised RECIST v1.1). (Ewing sarcoma and osteosarcoma) III. 1- and 2-year progression-free survival. (Ewing sarcoma and osteosarcoma) IV. 1- and 2-year overall survival. (Ewing sarcoma and osteosarcoma) V. Cabozantinib safety. (Ewing sarcoma and osteosarcoma) VI. To assess the ability of metabolic tumor response as measured by fludeoxyglucose (FDG)-positron emission tomography (PET) at the end of one cycle of treatment to predict progression-free survival (PFS). (Ewing sarcoma and osteosarcoma) VII. Translational research: to determine and compare tumor expression of MET, phosphorylated (phosphor)-MET and circulating levels of HGF, soluble MET (sMET), VEGF-A, and soluble VEGF receptor 2 (VEGFR2) (sVEGFR2) prior to and following administration of cabozantinib. (Ewing sarcoma and osteosarcoma)
OUTLINE:
Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
- Conditions
- Metastatic Ewing Sarcoma, Metastatic Osteosarcoma, Recurrent Ewing Sarcoma, Recurrent Osteosarcoma, Stage III Osteosarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7
- Being tested
- Cabozantinib S-malate, Laboratory Biomarker Analysis
- Medical subject headings
- Sarcoma, Ewing, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabozantinib S-malateDrug
Also called BMS-907351, Cabometyx, Cometriq, XL 184
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cabozantinib s-malate) | Experimental | Patients receive cabozantinib s-malate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-progression at 6 Months - Osteosarcoma
Non-progression defined as complete response (CR), partial response (PR), or stable disease (SD) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1.
As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
Measured: At 6 months
Objective Response Within 6 Months of Treatment Onset - Osteosarcoma
Objective response defined as complete response (CR) or partial response (PR) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1.
As per revised RECIST v1.1, CR is defined as disappearance of all target and non-target lesions and normalization of tumour marker level of non-target lesions. All lymph nodes must be non-pathological in size (<10 mm short axis).
As per revised RECIST v1.1, PR is defined as a at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and non-PD/not all evaluated non-target lesions, or, CR of target lesions and non-CR/non-PD/not evaluated non-target lesions.
As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
Measured: Within 6 months of treatment onset
Objective Response Within 6 Months of Treatment Onset - Ewing Sarcoma
Objective response defined as complete response (CR) or partial response (PR) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1.
As per revised RECIST v1.1, CR is defined as disappearance of all target and non-target lesions and normalization of tumour marker level of non-target lesions. All lymph nodes must be non-pathological in size (<10 mm short axis).
As per revised RECIST v1.1, PR is defined as a at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and non-PD/not all evaluated non-target lesions, or, CR of target lesions and non-CR/non-PD/not evaluated non-target lesions.
As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
Measured: Within 6 months of treatment onset
Secondary outcomes (5)
Best Overall Response
Best objective response rate, defined as the rate of CR or PR confirmed ≥ 4 weeks after initial documentation, as determined by investigator review of tumor assessments using RECIST v1.1. Complete or partial responses may be claimed only if the criteria for each are met at a subsequent time point as specified in the protocol (generally 4 weeks later). The BOR is the best response recorded from the start of the study treatment until the end of treatment
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
- Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm
- Stable Disease (SD): Neither sufficient shrinkage to qualify for PR
Measured: From the start of the treatment until disease progression/recurrence. assessed up to 2 years.
Progression Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression (clinical and/or radiological) or death, whichever occurs first. Radiological progression is assessed by local review of tumor assessments using RECIST v1.1 criteria : at least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm.
Measured: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
Overall Survival (OS)
OS is defined as the duration of time from start of treatment to the time of death.
Measured: Time from start of treatment to the time of death, assessed up to 2 years
Non-progression at 6 Months - Ewing Sarcoma
Non-progression defined as complete response (CR), partial response (PR), or stable disease (SD) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1.
As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
Measured: At 6 months
Incidence of Adverse Events
Number of patients who had at least one adverse event related to the treatment. Adverse events were assessed using CTCAE (5.0).
Measured: Safety profile was continuously followed during treatment and up to 30 days after the last Cabozantinib dose or until the start of a new antitumor therapy, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2014 (estimated)
- Study start19 Dec 2014
- Primary completion30 Jun 2019
- Study completion23 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic Ewing SarcomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Antoine Italiano, Principal investigator, Institut Bergonie Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02243605
- Sponsor's protocol ID
- NCI-2014-01927
- Other IDs
- NCI-2014-01927, CABONE, 9620, 9620
- Status last verified
- Jun 2026
- First submitted
- 16 Sep 2014
- Last updated
- 18 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E, Chevreau C, Duffaud F, Entz-Werle N, Saada E, Ray-Coquard I, Lervat C, Gaspar N, Marec-Berard P, Pacquement H, Wright J, Toulmonde M, Bessede A, Crombe A, Kind M, Bellera C, Blay JY. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):446-455. doi: 10.1016/S1470-2045(19)30825-3. Epub 2020 Feb 17.
PubMed 32078813Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of XL184 (Cabozantinib) in Treating Patients With Relapsed Osteosarcomas and Ewing Sarcomas
- ClinicalTrials.gov ID
- NCT02243605
- Acronym / sponsor ID
- NCI-2014-01927
- Conditions
- Metastatic Ewing Sarcoma, Metastatic Osteosarcoma, Recurrent Ewing Sarcoma, Recurrent Osteosarcoma, Stage III Osteosarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Dec 2014 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 23 Jul 2027 (estimated)
- First posted
- 18 Sep 2014 (estimated)
- Results
- Posted 4 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well cabozantinib s-malate works in treating patients with osteosarcoma or Ewing sarcoma that has grown or returned (come back) after a period of improvement. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may also prevent the growth of new blood vessels that tumors need to grow.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the antitumor activity of cabozantinib s-malate (cabozantinib) for Ewing sarcomas, in terms of 6-month objectives response as per the Response Evaluation Criteria in Solid Tumors, Revised (RECIST version [v]1.1).
II. To evaluate the antitumor activity of cabozantinib for osteosarcoma, in terms of 6-month objective response (complete response, partial response) and 6-month non-progression (complete response, partial response and stable disease), as per RECIST v1.1.
SECONDARY OBJECTIVES:
- 6-month objective response. (Ewing sarcoma only) II. Best overall response (as per the revised RECIST v1.1). (Ewing sarcoma and osteosarcoma) III. 1- and 2-year progression-free survival. (Ewing sarcoma and osteosarcoma) IV. 1- and 2-year overall survival. (Ewing sarcoma and osteosarcoma) V. Cabozantinib safety. (Ewing sarcoma and osteosarcoma) VI. To assess the ability of metabolic tumor response as measured by fludeoxyglucose (FDG)-positron emission tomography (PET) at the end of one cycle of treatment to predict progression-free survival (PFS). (Ewing sarcoma and osteosarcoma) VII. Translational research: to determine and compare tumor expression of MET, phosphorylated (phosphor)-MET and circulating levels of HGF, soluble MET (sMET), VEGF-A, and soluble VEGF receptor 2 (VEGFR2) (sVEGFR2) prior to and following administration of cabozantinib. (Ewing sarcoma and osteosarcoma)
OUTLINE:
Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cabozantinib s-malate) | Experimental | Drug: Cabozantinib S-malate, Other: Laboratory Biomarker AnalysisPatients receive cabozantinib s-malate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (27 listed)
- Young patient age between 12 - 15 could be included in only 6 centers (Bordeaux, Lyon, Villejuif, Lille, Marseille and Paris)
- Patients must have histologically confirmed diagnosis of osteosarcoma or Ewing sarcoma by central review, except if the diagnosis was already confirmed by the RRePS (Reseau de Reference en Pathologie des Sarcomes et des Tissus Mous et des Visceres) network
- Relapsed disease after standard chemotherapy
- Patients must have measurable disease (lesion in previously irradiated field could be considered as measurable if progressive at inclusion) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with spiral computed tomography (CT) scan
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
Key exclusion criteria (59 listed)
- The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
- Prior treatment with cabozantinib
- Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment; systemic treatment with radionuclides within 6 weeks before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment; note: subjects with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
- The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cabozantinib S-malateAlso: BMS-907351, Cabometyx, Cometriq, XL 184Given PO | Drug | Treatment (cabozantinib s-malate) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (cabozantinib s-malate) |
Primary outcome
Non-progression at 6 Months - Osteosarcoma
Time frame: At 6 months
Non-progression defined as complete response (CR), partial response (PR), or stable disease (SD) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1. As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
Objective Response Within 6 Months of Treatment Onset - Osteosarcoma
Time frame: Within 6 months of treatment onset
Objective response defined as complete response (CR) or partial response (PR) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1. As per revised RECIST v1.1, CR is defined as disappearance of all target and non-target lesions and normalization of tumour marker level of non-target lesions. All lymph nodes must be non-pathological in size (<10 mm short axis). As per revised RECIST v1.1, PR is defined as a at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and non-PD/not all evaluated non-target lesions, or, CR of target lesions and non-CR/non-PD/not evaluated non-target lesions. As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
Objective Response Within 6 Months of Treatment Onset - Ewing Sarcoma
Time frame: Within 6 months of treatment onset
Objective response defined as complete response (CR) or partial response (PR) as per the Response Evaluation Criteria In Solid Tumors Criteria, revised RECIST v1.1. As per revised RECIST v1.1, CR is defined as disappearance of all target and non-target lesions and normalization of tumour marker level of non-target lesions. All lymph nodes must be non-pathological in size (<10 mm short axis). As per revised RECIST v1.1, PR is defined as a at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and non-PD/not all evaluated non-target lesions, or, CR of target lesions and non-CR/non-PD/not evaluated non-target lesions. As per revised RECIST v1.1, progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or a measurable increase in a non-target lesion, or the appearance of one or more new lesions.
5 secondary outcomes
Best Overall Response
Time frame: From the start of the treatment until disease progression/recurrence. assessed up to 2 years.
Progression Free Survival (PFS)
Time frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
Overall Survival (OS)
Time frame: Time from start of treatment to the time of death, assessed up to 2 years
Non-progression at 6 Months - Ewing Sarcoma
Time frame: At 6 months
Incidence of Adverse Events
Time frame: Safety profile was continuously followed during treatment and up to 30 days after the last Cabozantinib dose or until the start of a new antitumor therapy, whichever occurs first.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32078813Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E, Chevreau C, Duffaud F, Entz-Werle N, Saada E, Ray-Coquard I, Lervat C, Gaspar N, Marec-Berard P, Pacquement H, Wright J, Toulmonde M, Bessede A, Crombe A, Kind M, Bellera C, Blay JY. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):446-455. doi: 10.1016/S1470-2045(19)30825-3. Epub 2020 Feb 17.
- Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoine Italiano principal investigator
Institut Bergonie Cancer Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib S-malate and Laboratory Biomarker Analysis in people with Metastatic Ewing Sarcoma and Metastatic Osteosarcoma, run by National Cancer Institute (NCI) at 11 sites in France.
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 27 inclusion and 59 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: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. 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?
Yes. Results are posted in the registry (first posted 4 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Non-progression at 6 Months - Osteosarcoma (time frame: At 6 months). The study lists 3 primary outcomes in all. 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 NCT02243605, which also lists 2 linked publications.
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 18 Aug 2026.