Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma

NCT02243605 | Active Not Recruiting Phase 2 Results

• 3 other identifiers: NCI-2014-01927CABONE9620
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 11

Brief 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. 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.

Conditions

Stage IVB Osteosarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Unresectable Ewing Sarcoma; Unresectable Osteosarcoma; Recurrent Osteosarcoma; Stage III Osteosarcoma AJCC v7; Metastatic Ewing Sarcoma; Metastatic Osteosarcoma; Recurrent Ewing Sarcoma; Stage IVA Osteosarcoma AJCC v7

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Within 6 months of treatment onset

Secondary Outcomes (5)

• Best Overall Response

  From the start of the treatment until disease progression/recurrence. assessed up to 2 years.

• Progression Free Survival (PFS)

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

• Overall Survival (OS)

  Time from start of treatment to the time of death, assessed up to 2 years

• Non-progression at 6 Months - Ewing Sarcoma

  At 6 months

• Incidence of Adverse Events

  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.

Study Arms (1)

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.

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL 184, XL-184, XL184

Treatment (cabozantinib s-malate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabozantinib s-malate)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Life expectancy of greater than 3 months
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

Institut Bergonie Cancer Center

Bordeaux, 33076, France

Location

Centre Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambert

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital De La Timone

Marseille, 13385, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie Paris

Paris, 75005, France

Location

Institut de Cancerologie de l'Ouest-Rene Gauducheau

Saint-Herblain, 44805, France

Location

CHRU Strasbourg - Hospital Civil

Strasbourg, 67091, France

Location

Center Claudius Regaud

Toulouse, 31052, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (2)

• 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.

  PMID: 32078813 DERIVED

• Hattinger 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.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Sarcoma, Ewing; Osteosarcoma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Pr Italiano Antoine, Department of Medical Oncology
• Organization: Institut Bergonie

a.italiano@bordeaux.unicancer.fr

0524071947

Study Officials

• Antoine Italiano

  Institut Bergonie Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 18, 2014
• Study Start: December 19, 2014
• Primary Completion: June 30, 2019
• Study Completion (Estimated): July 11, 2026
• Last Updated: June 12, 2026
• Results First Posted: September 4, 2020

Record last verified: 2026-06

Locations

FR (11)