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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 November 2023
• Main ID: NCT02243605
• Date of registration: 16/09/2014
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma
• Scientific title: A Phase 2 Study of XL184 (Cabozantinib) in Treating Patients With Relapsed Osteosarcomas and Ewing Sarcomas
• Date of first enrolment: December 19, 2014
• Target sample size: 90
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02243605
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Antoine Italiano
• Affiliation: Institut Bergonie Cancer Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- 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)

Exclusion Criteria:

- 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


Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Unresectable Ewing Sarcoma

Metastatic Osteosarcoma

Stage III Osteosarcoma AJCC v7

Stage IVA Osteosarcoma AJCC v7

Unresectable Osteosarcoma

Recurrent Ewing Sarcoma

Stage IVB Osteosarcoma AJCC v7

Recurrent Osteosarcoma

Metastatic Ewing Sarcoma

Stage IV Osteosarcoma AJCC v7

Intervention(s)

Drug: Cabozantinib S-malate

Other: Laboratory Biomarker Analysis

Primary Outcome(s)

Objective Response Within 6 Months of Treatment Onset - Ewing Sarcoma [Time Frame: Within 6 months of treatment onset]

Objective Response Within 6 Months of Treatment Onset - Osteosarcoma [Time Frame: Within 6 months of treatment onset]

Non-progression at 6 Months - Osteosarcoma [Time Frame: At 6 months]

Secondary Outcome(s)

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]

Best Overall Response [Time Frame: From the start of the treatment until disease progression/recurrence, assessed up to 2 years]

Non-progression at 6 Months - Ewing Sarcoma [Time Frame: At 6 months]

Overall Survival (OS) [Time Frame: Time from start of treatment to the time of death, assessed up to 2 years]

Incidence of Adverse Events [Time Frame: Up to 2 years]

Secondary ID(s)

CABONE

9620

NCI-2014-01927

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/09/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02243605