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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT02243605
Collaborator
(none)
90
11
1
8.2

Study Details

Study Description

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.

Detailed Description

PRIMARY OBJECTIVES:
  1. 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).

  2. 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:
  1. 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

Study Type:
Interventional
Actual Enrollment :
90 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of XL184 (Cabozantinib) in Treating Patients With Relapsed Osteosarcomas and Ewing Sarcomas
Actual Study Start Date :
Dec 19, 2014
Actual Primary Completion Date :
Jun 30, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (cabozantinib s-malate)

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
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Non-progression at 6 Months - Osteosarcoma [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.

    2. Objective Response Within 6 Months of Treatment Onset - Osteosarcoma [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.

    3. Objective Response Within 6 Months of Treatment Onset - Ewing Sarcoma [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.

    Secondary Outcome Measures

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

      Will be analyzed independently for each stratum (osteosarcoma and Ewing sarcoma). Will be described using frequency, percentage, and 95% confidence interval (binomial law).

    2. Progression Free Survival (PFS) [Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years]

      Will be analyzed independently for each stratum (osteosarcoma and Ewing sarcoma). PFS will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method. Multivariate analyses can also be carried out based on Cox's proportional risk method and after checking the risk proportionality hypothesis.

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

      Will be analyzed independently for each stratum (osteosarcoma and Ewing sarcoma). OS will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method. Multivariate analyses can also be carried out based on Cox's proportional risk method and after checking the risk proportionality hypothesis.

    4. Incidence of Adverse Events [Up to 2 years]

      Will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Quantitative variables will be described using mean and standard errors if the normality assumption is satisfied, else other descriptive statistics (median, range, quartiles) will be used. Qualitative variables will be described using frequency, percentage, and 95% confidence interval.

    5. Non-progression at 6 Months - Ewing Sarcoma [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Institut Bergonie Cancer Center Bordeaux France 33076
    2 Centre Georges-Francois Leclerc Dijon France 21079
    3 Centre Oscar Lambert Lille France 59020
    4 Centre Leon Berard Lyon France 69373
    5 Hopital De La Timone Marseille France 13385
    6 Centre Antoine Lacassagne Nice France 06189
    7 Institut Curie Paris Paris France 75005
    8 Institut de Cancerologie de l'Ouest-Rene Gauducheau Saint Herblain France 44805
    9 CHRU Strasbourg - Hospital Civil Strasbourg France 67091
    10 Center Claudius Regaud Toulouse France 31052
    11 Gustave Roussy Villejuif France 94805

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Antoine Italiano, Institut Bergonie Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02243605
    Other Study ID Numbers:
    • NCI-2014-01927
    • NCI-2014-01927
    • CABONE
    • 9620
    • 9620
    First Posted:
    Sep 18, 2014
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    May 1, 2022
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ewing Sarcoma Osteosarcoma
    Arm/Group Description 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.
    Period Title: Stage 1 - Interim Analysis Population
    STARTED 23 22
    COMPLETED 21 21
    NOT COMPLETED 2 1
    Period Title: Stage 1 - Interim Analysis Population
    STARTED 45 45
    COMPLETED 39 42
    NOT COMPLETED 6 3

    Baseline Characteristics

    Arm/Group Title Ewing Sarcoma Osteosarcoma Total
    Arm/Group Description 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 of all reporting groups
    Overall Participants 45 45 90
    Age (Count of Participants)
    <=18 years
    6
    13.3%
    7
    15.6%
    13
    14.4%
    Between 18 and 65 years
    38
    84.4%
    31
    68.9%
    69
    76.7%
    >=65 years
    1
    2.2%
    7
    15.6%
    8
    8.9%
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    33
    34
    34
    Sex: Female, Male (Count of Participants)
    Female
    14
    31.1%
    18
    40%
    32
    35.6%
    Male
    31
    68.9%
    27
    60%
    58
    64.4%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    France
    45
    100%
    45
    100%
    90
    100%

    Outcome Measures

    1. Primary Outcome
    Title Non-progression at 6 Months - Osteosarcoma
    Description 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.
    Time Frame At 6 months

    Outcome Measure Data

    Analysis Population Description
    All patients eligible and who received at least one complete or two incomplete treatment cycles.
    Arm/Group Title Osteosarcoma
    Arm/Group Description 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.
    Measure Participants 42
    Number (95% Confidence Interval) [percentage]
    33.3
    2. Primary Outcome
    Title Objective Response Within 6 Months of Treatment Onset - Osteosarcoma
    Description 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.
    Time Frame Within 6 months of treatment onset

    Outcome Measure Data

    Analysis Population Description
    All patients eligible and who received at least one complete or two incomplete treatment cycles.
    Arm/Group Title Osteosarcoma
    Arm/Group Description 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.
    Measure Participants 42
    Number (95% Confidence Interval) [percentage]
    11.9
    3. Primary Outcome
    Title Objective Response Within 6 Months of Treatment Onset - Ewing Sarcoma
    Description 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.
    Time Frame Within 6 months of treatment onset

    Outcome Measure Data

    Analysis Population Description
    All patients eligible and who received at least one complete or two incomplete treatment cycles.
    Arm/Group Title Ewing Sarcoma
    Arm/Group Description 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.
    Measure Participants 39
    Number (95% Confidence Interval) [percentage]
    25.6
    4. Secondary Outcome
    Title Best Overall Response
    Description Will be analyzed independently for each stratum (osteosarcoma and Ewing sarcoma). Will be described using frequency, percentage, and 95% confidence interval (binomial law).
    Time Frame From the start of the treatment until disease progression/recurrence, assessed up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description Will be analyzed independently for each stratum (osteosarcoma and Ewing sarcoma). PFS will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method. Multivariate analyses can also be carried out based on Cox's proportional risk method and after checking the risk proportionality hypothesis.
    Time Frame Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    Title Overall Survival (OS)
    Description Will be analyzed independently for each stratum (osteosarcoma and Ewing sarcoma). OS will be analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method. Multivariate analyses can also be carried out based on Cox's proportional risk method and after checking the risk proportionality hypothesis.
    Time Frame Time from start of treatment to the time of death, assessed up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    Title Incidence of Adverse Events
    Description Will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Quantitative variables will be described using mean and standard errors if the normality assumption is satisfied, else other descriptive statistics (median, range, quartiles) will be used. Qualitative variables will be described using frequency, percentage, and 95% confidence interval.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    Title Non-progression at 6 Months - Ewing Sarcoma
    Description 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.
    Time Frame At 6 months

    Outcome Measure Data

    Analysis Population Description
    All patients eligible and who received at least one complete or two incomplete treatment cycles.
    Arm/Group Title Ewing Sarcoma
    Arm/Group Description 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.
    Measure Participants 39
    Number (95% Confidence Interval) [percentage]
    25.6

    Adverse Events

    Time Frame Osteosarcoma : 26 months of treatment. At the time of primary analysis, 3 were still on treatment and 42 patients discontinued treatment. Ewing sarcoma : 20 months of treatment. At the time of primary analysis, 3 were still on treatment and 42 patients discontinued treatment.
    Adverse Event Reporting Description 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.
    Arm/Group Title Osteosarcoma Ewing Sarcoma
    Arm/Group Description 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.
    All Cause Mortality
    Osteosarcoma Ewing Sarcoma
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 34/45 (75.6%) 30/45 (66.7%)
    Serious Adverse Events
    Osteosarcoma Ewing Sarcoma
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/45 (66.7%) 31/45 (68.9%)
    Blood and lymphatic system disorders
    Anemia 1/45 (2.2%) 1 2/45 (4.4%) 2
    Febrile neutropenia 0/45 (0%) 0 1/45 (2.2%) 1
    Cardiac disorders
    Pericardial effusion 2/45 (4.4%) 2 1/45 (2.2%) 1
    Cardiac disorders - Other, specify 1/45 (2.2%) 1 0/45 (0%) 0
    Gastrointestinal disorders
    Constipation 0/45 (0%) 0 1/45 (2.2%) 1
    Rectal hemorrhage 1/45 (2.2%) 1 0/45 (0%) 0
    Gastrointestinal disorders - Other, specify 1/45 (2.2%) 1 0/45 (0%) 0
    General disorders
    Death NOS 0/45 (0%) 0 1/45 (2.2%) 1
    Fatigue 1/45 (2.2%) 1 0/45 (0%) 0
    Fever 1/45 (2.2%) 1 1/45 (2.2%) 1
    General disorders and administration site conditions - Other, specify 2/45 (4.4%) 2 3/45 (6.7%) 3
    Disease progression 2/45 (4.4%) 2 4/45 (8.9%) 4
    Hepatobiliary disorders
    Hepatobiliary disorders - Other, specify 0/45 (0%) 0 1/45 (2.2%) 1
    Infections and infestations
    Anorectal infection 0/45 (0%) 0 1/45 (2.2%) 1
    Bronchial infection 1/45 (2.2%) 1 0/45 (0%) 0
    Kidney infection 0/45 (0%) 0 1/45 (2.2%) 1
    Sepsis 2/45 (4.4%) 2 0/45 (0%) 0
    Soft tissue infection 1/45 (2.2%) 1 0/45 (0%) 0
    Infections and infestations - Other, specify 0/45 (0%) 0 1/45 (2.2%) 1
    Injury, poisoning and procedural complications
    Wound complication 0/45 (0%) 0 1/45 (2.2%) 1
    Investigations
    GGT increased 0/45 (0%) 0 1/45 (2.2%) 1
    Lipase increased 1/45 (2.2%) 1 1/45 (2.2%) 1
    Lymphocyte count decreased 1/45 (2.2%) 1 0/45 (0%) 0
    Neutrophil count decreased 1/45 (2.2%) 1 0/45 (0%) 0
    Platelet count decreased 0/45 (0%) 0 1/45 (2.2%) 1
    Investigations - Other, specify 0/45 (0%) 0 1/45 (2.2%) 1
    Metabolism and nutrition disorders
    Hypomagnesemia 1/45 (2.2%) 1 0/45 (0%) 0
    Metabolism and nutrition disorders - Other, specify 1/45 (2.2%) 1 0/45 (0%) 0
    Musculoskeletal and connective tissue disorders
    Bone pain 0/45 (0%) 0 5/45 (11.1%) 5
    Chest wall pain 0/45 (0%) 0 1/45 (2.2%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 1/45 (2.2%) 1 0/45 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 3/45 (6.7%) 3 2/45 (4.4%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 1/45 (2.2%) 1 1/45 (2.2%) 1
    Nervous system disorders
    Peripheral motor neuropathy 1/45 (2.2%) 1 0/45 (0%) 0
    Nervous system disorders - Other, specify 1/45 (2.2%) 1 0/45 (0%) 0
    Spinal cord compression 1/45 (2.2%) 1 3/45 (6.7%) 3
    Psychiatric disorders
    Psychiatric disorders - Other, specify 0/45 (0%) 0 1/45 (2.2%) 1
    Renal and urinary disorders
    Acute kidney injury 1/45 (2.2%) 1 0/45 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 2/45 (4.4%) 2 2/45 (4.4%) 2
    Epistaxis 1/45 (2.2%) 1 0/45 (0%) 0
    Pleural effusion 7/45 (15.6%) 7 2/45 (4.4%) 2
    Pneumothorax 11/45 (24.4%) 11 14/45 (31.1%) 14
    Respiratory, thoracic and mediastinal disorders - Other, specify 1/45 (2.2%) 1 3/45 (6.7%) 3
    Skin and subcutaneous tissue disorders
    Skin ulceration 2/45 (4.4%) 2 0/45 (0%) 0
    Vascular disorders
    Thromboembolic event 2/45 (4.4%) 2 0/45 (0%) 0
    Other (Not Including Serious) Adverse Events
    Osteosarcoma Ewing Sarcoma
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 45/45 (100%) 45/45 (100%)
    Blood and lymphatic system disorders
    Anemia 6/45 (13.3%) 7 8/45 (17.8%) 10
    Cardiac disorders
    Sinus tachycardia 3/45 (6.7%) 3 4/45 (8.9%) 4
    Endocrine disorders
    Hypothyroidism 23/45 (51.1%) 25 21/45 (46.7%) 23
    Eye disorders
    Blurred vision 1/45 (2.2%) 1 4/45 (8.9%) 4
    Gastrointestinal disorders
    Abdominal pain 8/45 (17.8%) 10 12/45 (26.7%) 12
    Constipation 14/45 (31.1%) 20 14/45 (31.1%) 19
    Diarrhea 30/45 (66.7%) 45 33/45 (73.3%) 46
    Dry mouth 1/45 (2.2%) 1 7/45 (15.6%) 7
    Dysphagia 2/45 (4.4%) 2 3/45 (6.7%) 3
    Gastroesophageal reflux disease 4/45 (8.9%) 4 7/45 (15.6%) 8
    Gastrointestinal pain 2/45 (4.4%) 2 3/45 (6.7%) 3
    Hemorrhoids 2/45 (4.4%) 2 3/45 (6.7%) 3
    Mucositis oral 25/45 (55.6%) 30 24/45 (53.3%) 29
    Nausea 19/45 (42.2%) 22 15/45 (33.3%) 18
    Toothache 3/45 (6.7%) 3 2/45 (4.4%) 2
    Vomiting 7/45 (15.6%) 9 10/45 (22.2%) 12
    Gastrointestinal disorders - Other, specify 12/45 (26.7%) 13 9/45 (20%) 11
    General disorders
    Fatigue 34/45 (75.6%) 41 32/45 (71.1%) 36
    Fever 8/45 (17.8%) 11 7/45 (15.6%) 8
    Non-cardiac chest pain 8/45 (17.8%) 11 3/45 (6.7%) 3
    Pain 8/45 (17.8%) 9 7/45 (15.6%) 8
    General disorders and administration site conditions - Other, specify 6/45 (13.3%) 6 4/45 (8.9%) 4
    Disease progression 2/45 (4.4%) 2 4/45 (8.9%) 4
    Infections and infestations
    Bronchial infection 4/45 (8.9%) 7 3/45 (6.7%) 3
    Pharyngitis 1/45 (2.2%) 1 4/45 (8.9%) 4
    Rhinitis infective 4/45 (8.9%) 4 1/45 (2.2%) 1
    Skin infection 1/45 (2.2%) 1 3/45 (6.7%) 3
    Infections and infestations - Other, specify 8/45 (17.8%) 8 6/45 (13.3%) 7
    Injury, poisoning and procedural complications
    Fall 3/45 (6.7%) 3 0/45 (0%) 0
    Investigations
    Alanine aminotransferase increased 21/45 (46.7%) 25 22/45 (48.9%) 27
    Alkaline phosphatase increased 6/45 (13.3%) 6 7/45 (15.6%) 9
    Aspartate aminotransferase increased 23/45 (51.1%) 28 22/45 (48.9%) 27
    Blood bilirubin increased 3/45 (6.7%) 3 3/45 (6.7%) 3
    CPK increased 1/45 (2.2%) 1 4/45 (8.9%) 6
    Electrocardiogram QT corrected interval prolonged 4/45 (8.9%) 4 0/45 (0%) 0
    GGT increased 2/45 (4.4%) 2 5/45 (11.1%) 5
    Lipase increased 9/45 (20%) 16 4/45 (8.9%) 5
    Lymphocyte count decreased 3/45 (6.7%) 5 3/45 (6.7%) 5
    Neutrophil count decreased 9/45 (20%) 11 10/45 (22.2%) 11
    Platelet count decreased 13/45 (28.9%) 13 19/45 (42.2%) 21
    Serum amylase increased 4/45 (8.9%) 4 2/45 (4.4%) 2
    Weight loss 14/45 (31.1%) 14 14/45 (31.1%) 14
    White blood cell decreased 3/45 (6.7%) 5 5/45 (11.1%) 7
    Investigations - Other, specify 2/45 (4.4%) 4 5/45 (11.1%) 5
    Blood lactate dehydrogenase increased 5/45 (11.1%) 7 5/45 (11.1%) 6
    Thyroid stimulating hormone increased 6/45 (13.3%) 6 4/45 (8.9%) 4
    Metabolism and nutrition disorders
    Anorexia 23/45 (51.1%) 27 11/45 (24.4%) 13
    Hypoalbuminemia 3/45 (6.7%) 3 3/45 (6.7%) 3
    Hypocalcemia 6/45 (13.3%) 9 3/45 (6.7%) 4
    Hypokalemia 8/45 (17.8%) 14 4/45 (8.9%) 4
    Hypomagnesemia 12/45 (26.7%) 18 6/45 (13.3%) 7
    Hypophosphatemia 11/45 (24.4%) 12 15/45 (33.3%) 21
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/45 (6.7%) 3 4/45 (8.9%) 4
    Back pain 8/45 (17.8%) 8 12/45 (26.7%) 15
    Bone pain 1/45 (2.2%) 1 9/45 (20%) 9
    Myalgia 6/45 (13.3%) 7 6/45 (13.3%) 8
    Pain in extremity 3/45 (6.7%) 3 1/45 (2.2%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 9/45 (20%) 9 5/45 (11.1%) 6
    Muscle cramp 0/45 (0%) 0 3/45 (6.7%) 4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 8/45 (17.8%) 10 4/45 (8.9%) 5
    Nervous system disorders
    Dysgeusia 9/45 (20%) 10 14/45 (31.1%) 14
    Headache 7/45 (15.6%) 10 10/45 (22.2%) 12
    Nervous system disorders - Other, specify 4/45 (8.9%) 5 0/45 (0%) 0
    Spinal cord compression 0/45 (0%) 0 4/45 (8.9%) 4
    Psychiatric disorders
    Anxiety 5/45 (11.1%) 5 2/45 (4.4%) 2
    Depression 5/45 (11.1%) 5 2/45 (4.4%) 2
    Insomnia 6/45 (13.3%) 6 2/45 (4.4%) 2
    Renal and urinary disorders
    Proteinuria 6/45 (13.3%) 8 4/45 (8.9%) 5
    Renal and urinary disorders - Other, specify 3/45 (6.7%) 3 0/45 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 11/45 (24.4%) 14 10/45 (22.2%) 12
    Dyspnea 12/45 (26.7%) 12 7/45 (15.6%) 8
    Epistaxis 8/45 (17.8%) 8 4/45 (8.9%) 5
    Pleural effusion 9/45 (20%) 10 3/45 (6.7%) 3
    Pneumothorax 10/45 (22.2%) 11 10/45 (22.2%) 15
    Voice alteration 10/45 (22.2%) 11 4/45 (8.9%) 4
    Respiratory, thoracic and mediastinal disorders - Other, specify 7/45 (15.6%) 7 5/45 (11.1%) 6
    Skin and subcutaneous tissue disorders
    Alopecia 6/45 (13.3%) 6 6/45 (13.3%) 6
    Dry skin 13/45 (28.9%) 14 16/45 (35.6%) 18
    Erythema multiforme 4/45 (8.9%) 5 5/45 (11.1%) 5
    Palmar-plantar erythrodysesthesia syndrome 14/45 (31.1%) 14 18/45 (40%) 21
    Rash acneiform 3/45 (6.7%) 3 1/45 (2.2%) 1
    Rash maculo-papular 4/45 (8.9%) 4 1/45 (2.2%) 1
    Skin hypopigmentation 5/45 (11.1%) 5 5/45 (11.1%) 5
    Skin ulceration 6/45 (13.3%) 8 2/45 (4.4%) 2
    Skin and subcutaneous tissue disorders - Other, specify 22/45 (48.9%) 34 9/45 (20%) 14
    Hair color changes 15/45 (33.3%) 15 15/45 (33.3%) 15
    Vascular disorders
    Hypertension 7/45 (15.6%) 9 3/45 (6.7%) 3
    Thromboembolic event 5/45 (11.1%) 5 0/45 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Pr Italiano Antoine, Department of Medical Oncology
    Organization Institut Bergonie
    Phone 0524071947
    Email a.italiano@bordeaux.unicancer.fr
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02243605
    Other Study ID Numbers:
    • NCI-2014-01927
    • NCI-2014-01927
    • CABONE
    • 9620
    • 9620
    First Posted:
    Sep 18, 2014
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    May 1, 2022