Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Osteosarcoma

Sarcoma

Sarcoma, Ewing

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

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.

Cabozantinib S-malate

Laboratory Biomarker Analysis

Antoine Italiano

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.

PRIMARY OBJECTIVES:

I. 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:

I. 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.

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

A Phase 2 Study of XL184 (Cabozantinib) in Treating Patients With Relapsed Osteosarcomas and Ewing Sarcomas

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 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.

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

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.

OS is defined as the duration of time from start of treatment to the time of death.

Number of patients who had at least one adverse event related to the treatment. Adverse events were assessed using CTCAE (5.0).

National Cancer Institute (NCI)

Adverse event are reported for all treated patients who received at least one administration of treatment.

All adverse events (related and unrelated to treatment) are reported. All serious adverse events (related and unrelated to treatment) are reported.

Patients receive cabozantinib s-malate PO QD on days 1-28. 60 mg for patients ≥ 16 years and 40mg/m² for patients ≥ 12 years and \<16 years. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive cabozantinib s-malate PO QD on days 1-28. 60 mg for patients ≥ 16 years and 40mg/m² for patients ≥ 12 years and \<16 years. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Single-arm phase II clinical trial based on a two-stage optimal Simon's design with 41 evaluable patients (first stage: 21 patients) used to distinguish a favorable true objective response rate within 6 months of treatment onset of 20% from a null rate of 5% (90% power and 5% type I error).

Stage 1(21 evaluable patients): if \<=1 objective response within 6 months of treatment onset, the study was stopped early. Otherwise, the second group of 20 participants was recruited.

Stage 2 (41 evaluable patients): if \>= 5 objective response within 6 months of treatment onset, Cabozantinib was considered promising.

Patients receive cabozantinib s-malate PO QD on days 1-28. 60 mg for patients ≥ 16 years and 40mg/m² for patients ≥ 12 years and \<16 years. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Single-arm phase II trial based on 2-stage dual endpoint design with 41 evaluable patients (first stage: 21 patients) used to distinguish :

* a favorable true 6-month non-progression rate of 50% from a null rate of 25% (92% power).
* a favorable true objective response rate within 6 months of treatment onset of 20% from a null rate of 5% (90% power).

Stage 1(21 evaluable patients): if \<=1 objective response within 6 months of treatment onset or \<=6 6-month non-progression, the study was stopped early. Otherwise, the second group of 20 participants was recruited.

Stage 2 (41 evaluable patients): if \>= 5 objective response within 6 months of treatment onset or \>=16 6-month non-progression, Cabozantinib was considered promising.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

France

Region of Enrollment

Pr Italiano Antoine, Department of Medical Oncology

All patients eligible and who received at least one complete or two incomplete treatment cycles.

Non-progression at 6 Months - Osteosarcoma

Objective Response Within 6 Months of Treatment Onset - Osteosarcoma

Objective Response Within 6 Months of Treatment Onset - Ewing Sarcoma

Best Overall Response

Progression Free Survival (PFS)

Overall Survival (OS)

Non-progression at 6 Months - Ewing Sarcoma

Adverse event are reported for all treated patients who received at least one administration of treatment.

Spots Global Cancer Trial Database for unresectable osteosarcoma