Ewing SarcomaPhase 1NCT06156410
Cabozantinib With Ifosfamide in Relapsed/Refractory Sarcomas
A Phase 1 study testing Cabozantinib in people with Ewing Sarcoma and Osteosarcoma, run by Children's Hospital of Philadelphia at 4 sites in United States.
Trial summary
The purpose of this study is to better understand how safe and effective the drug cabozantinib in combination with high-dose ifosfamide is in the treatment of children and adults with relapsed/refractory sarcomas. Read more about this study
- Who is it for?
- Ages 5 to 40 years
- Conditions the study is for
- Ewing Sarcoma, Osteosarcoma, Sarcomas
- What is being tested?
- Cabozantinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 24 Oct 2023to Nov 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 5 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologic diagnosis of any sarcoma, including bone and soft tissue sarcomas. Biopsy from current relapse/progression is highly preferred, though will accept tissue from prior relapse/progression or initial diagnosis with approval from the study Principal Investigator or designee.
- Disease that has progressed on or relapsed after upfront initial therapy, which must have included traditional chemotherapy.
- Evaluable or Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1), within 21 days of enrollment.
- Age, within the following parameters by cohort:
- Phase I dose-finding cohort: age 12 to 40 years at the time of enrollment.
- Phase I dose-confirmation cohort: age 5 to < 12 years at the time of enrollment.
Show all 26Show fewer
- Body surface area (BSA): > 0.35 m2.
- Performance status: Lansky play (< 16 years of age) or Karnofsky (> 16 years of age) of ≥ 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories < 2.
- Prior toxicity: recovery to baseline or grade < 1, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0), from all acute toxicities, unless adverse events (AE) are clinically non-significant (i.e. alopecia) or controlled on supportive care (i.e. nausea/vomiting, hypothyroidism).
- Able to swallow tablets whole.
- Hematopoietic function:
- Absolute neutrophil count > 1,000/uL (without hematopoietic growth factor within the time frame noted below).
- Hemoglobin > 8 g/dL (without transfusion in the last 7 days).
- Platelets > 100,000/uL (without transfusion in the last 7 days).
- Renal function:
- Normal renal function determined by one of the following means (even if others are outside of normal range): 1) serum creatinine < 1.5 x upper limit of normal (ULN) for age; 2) cystatin C within normal limits; 3) nuclear medicine glomerular filtration rate (GFR) within normal limits, or 4) calculated creatinine clearance of > 70 mL/min/1.73 m2 (≥ 1.17mL/sec)
- Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-hour urine protein ≤ 1 g.
- Hepatic function:
- Total bilirubin < 1.5 x ULN (for subjects with Gilbert's disease < 3.0 x ULN).
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN (ALP ≤ 5 x ULN is allowed with documented bone metastases). For the purpose of this study, the ULN for ALT is defined as 45 IU/L.
- Serum albumin > 2.8 g/dL.
- Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.3 x ULN.
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (i.e. barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.
- Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met:
- Pre-pubertal by tanner staging, defined as Tanner stage 1 or 2.
- Documented permanent sterilization (i.e. hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). Documentation of permanent sterilization or postmenopausal status may include review of medical records, medical examinations, or medical history interview by study site.
Who cannot join
- Radiographic evidence of tumor invading major blood vessels, or endotracheal or endobronchial tumor.
- Radiographic evidence of tumor invading the gastrointestinal tract, including esophagus, stomach, small or large bowel, rectum, or anus.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy or surgery (including radiosurgery) and stable for at least 4 weeks prior to enrollment after radiotherapy or major surgery (i.e. removal or biopsy of brain metastasis). Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
- Prior progression/relapse with cabozantinib. Prior therapy with cabozantinib without progression/relapse and prior use of other multi-tyrosine kinase inhibitors is allowed.
- Prior therapy with high-dose ifosfamide (> 10 g/m2/cycle) at any point.
- Any small molecule inhibitor therapy within 5 half-lives of the drug or 14 days, whichever is shorter, before enrollment.
Show all 41Show fewer
- Myelosuppressive chemotherapy within 14 days before enrollment.
- Autologous bone marrow transplant (auto-BMT) within 42 days before enrollment.
- Immunotherapy, including chimeric antigen receptor T-cells (CAR-T), within 21 days before enrollment.
- Small port radiation therapy within 14 days before enrollment. Substantial bone marrow radiation (i.e. > 50% of the pelvis) or craniospinal radiation within 4 weeks before enrollment. Subjects with any clinically relevant ongoing complications from prior radiation therapy should not be treated with cabozantinib until these complications have resolved.
- Major surgery (i.e. abdominal surgery; excluding intracranial surgery as noted above) within 14 days before enrollment. Minor surgeries (including mediport or tunneled catheter placement; excluding needle biopsy for tumor sampling or peripherally inserted central catheter placement) within 10 days before enrollment. Subjects must have documented complete wound healing from major surgery or minor surgery before enrollment.
- Hematopoietic growth factors within 7 days (for short-acting growth factor) or 14 days (for long-acting growth factor) before enrollment.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations. See Table 10 in Section 9.1.4 for components of cabozantinib.
- History of clinically significant hemorrhagic cystitis, defined as grade > 3 non-infectious cystitis, associated with antineoplastic agents.
- Any medications that are strong CYP3A4 inducers or inhibitors or medications definitely known to cause QTc prolongation.
- Concomitant anticoagulation with coumarin agents (i.e. warfarin), direct thrombin inhibitors (i.e. dabigatran), certain direct factor Xa inhibitors (betrixaban), or platelet inhibitors (i.e. clopidogrel). Allowed anticoagulants are the following:
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- Therapeutic doses of LMWH and certain direct factor Xa inhibitors (rivaroxaban, edoxaban, apixaban) in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before enrollment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
- Cardiovascular disease, including:
- Class III or IV congestive heart failure (New York Heart Association grading).
- Congenital prolonged QT syndrome, clinically significant cardiac arrhythmia, or prolonged corrected QT (QTc) within 14 days before enrollment.
- Uncontrolled hypertension, defined as sustained blood pressure > 95th percentile for age, height, and gender for pediatric subjects and > 140/90 mmHg for adult subjects, despite optimal antihypertensive treatment.
- Stroke, transient ischemic attack (TIA), myocardial infarction (MI), unstable angina pectoris, or other ischemic or thromboembolic event (excluding those associated with a central line) within 6 months before enrollment.
- Gastrointestinal disease, including:
- Active peptic ulcer disease, inflammatory bowel disease (Crohn's disease, ulcerative colitis), diverticulitis, cholecystitis, symptomatic cholangitis, appendicitis, or acute pancreatitis.
- Acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
- Intra-abdominal abscess within 6 months before enrollment. Complete healing of an intra-abdominal abscess must be confirmed before enrollment.
- Any other condition associated with a high risk of perforation, fistula formation, or potential for decreased absorption of cabozantinib, such as tumors invading the GI tract and ongoing visceral complications from prior radiation therapy.
- Bleeding conditions, including:
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (i.e. pulmonary hemorrhage) within 12 weeks before enrollment.
- Radiographic evidence of acute intracranial hemorrhage. In the absence of clinical symptoms, a baseline CT/MRI brain need not be obtained.
- Any other active malignancy at time of enrollment or diagnosis of another malignancy within 3 years prior to enrollment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
- Other clinically significant disorders that would preclude safe study participation, including:
- Cavitating pulmonary lesion.
- Serious non-healing wound/ulcer/bone fracture.
- Uncompensated/symptomatic hypothyroidism.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
- Recipient of solid organ transplant, known human immunodeficiency virus (HIV) seropositivity, and other non-treatment related immunodeficiencies.
- Severe or uncontrolled infection or systemic disease.
- Inadequate electrolyte balance, defined as abnormal levels of serum potassium, calcium, magnesium, and phosphorous and causing clinically significant symptoms, acid-base disturbances, or changes in ECG.
- Women who are currently pregnant or breastfeeding.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Emily Blauel, MD, 720-777-6978, Emily.Blauel@childrenscolorado.org
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Shelby Brizzolara Dove, 267-425-2187, 22ST012@chop.edu
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Daniel Lefler, MD, 215-829-7089, SarcomaResearch@uphs.upenn.edu
- Recruiting
University of California San Francisco
San Francisco, California, 94143
Benjamin Lerman, MD, 877-827-3222, cancertrials@ucsf.edu
Benjamin Lerman
About this study
Official title: A Phase I Trial of Cabozantinib (XL184) in Combination With High-dose Ifosfamide in Adults and Children With Relapsed/Refractory Sarcomas (CaIRS Trial)
The purpose of this study is to better understand how safe and effective the drug cabozantinib in combination with high-dose ifosfamide is in the treatment of children and adults with relapsed/refractory sarcomas.
Read the detailed description
In this study, the investigators will test the activity of cabozantinib in combination with high-dose ifosfamide as targeted therapy for relapsed/refractory sarcomas. Cabozantinib has been shown to inhibit multiple tyrosine kinases, including potent inhibition of kinases, MET and VEGFR2. Therefore, the goal of this study is to see if Cabozantinib can be used to inhibit MET and VEGFR2, or other tyrosine kinases to drive tumor responses in patients.
- Conditions
- Ewing Sarcoma, Osteosarcoma, Sarcomas
- Being tested
- Cabozantinib
- Keywords
- relapsed, refractory
- Medical subject headings
- Sarcoma, Ewing, Osteosarcoma, Sarcoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Participants will receive cabozantinib in combination with high-dose ifosfamide for 5 cycles. If still on study therapy the participants will continue with cabozantinib monotherapy for up to 12 total cycles.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Cabozantinib Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of cabozantinib
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0).
Measured: Upon completion of accrual to phase 1 cohort, approximately 1 year
Secondary outcomes (5)
Toxicity profile
Define and describe the toxicity profile (grade 2 and above) of cabozantinib administered in combination with high-dose ifosfamide using Common Terminology Criteria for Adverse Events (CTCAE).
Measured: Upon completion of trial, approximately 1 year
Dose-limiting toxicities (DLT)
Define and describe the dose-limiting toxicities (DLT) of cabozantinib administered in combination with high-dose ifosfamide using Common Terminology Criteria for Adverse Events (CTCAE).
Measured: After two cycles of treatment, average 56 days (one cycle is 28 days)
Antitumor activity Ewing sarcoma
Evaluate the antitumor activity of cabozantinib administered in combination with high-dose ifosfamide for relapsed/refractory Ewing sarcoma using the Response Criteria for Patients with Solid Tumors (RECIST) scale. Disease progression will be measured periodically while on study.
Measured: 6 months
Antitumor activity osteosarcoma
Evaluate the antitumor activity of cabozantinib administered in combination with high-dose ifosfamide for relapsed/refractory osteosarcoma using the Response Criteria for Patients with Solid Tumors (RECIST) scale. Disease progression will be measured periodically while on study.
Measured: 6 months
Antitumor Activity Relapsed/Refractory Sarcomas
Evaluate the antitumor activity of cabozantinib administered in combination with high-dose ifosfamide for relapsed/refractory sarcomas using the Response Criteria for Patients with Solid Tumors (RECIST) scale. Disease progression will be measured periodically while on study.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2023
- Study start24 Oct 2023
- Primary completionNov 2027 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ewing SarcomaStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Colorado, Alex's Lemonade Stand Foundation, Exelixis
- Responsible party
- Sponsor
- Investigators
- Theodore Laetsch, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06156410
- Sponsor's protocol ID
- 22-019876
- Status last verified
- Sep 2026
- First submitted
- 10 Nov 2023
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Children's Hospital of Philadelphia, as the sponsor and lead site for this trial, will have access to all participant data throughout the study. Certain biological samples will be sent to the University of Colorado for processing and analysis.
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Cabozantinib (XL184) in Combination With High-dose Ifosfamide in Adults and Children With Relapsed/Refractory Sarcomas (CaIRS Trial)
- ClinicalTrials.gov ID
- NCT06156410
- Acronym / sponsor ID
- 22-019876
- Conditions
- Ewing Sarcoma, Osteosarcoma, Sarcomas
- Keywords
- relapsed, refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Children's Hospital Colorado, Alex's Lemonade Stand Foundation, Exelixis
- Study start
- 24 Oct 2023 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 5 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to better understand how safe and effective the drug cabozantinib in combination with high-dose ifosfamide is in the treatment of children and adults with relapsed/refractory sarcomas.
Detailed description
In this study, the investigators will test the activity of cabozantinib in combination with high-dose ifosfamide as targeted therapy for relapsed/refractory sarcomas. Cabozantinib has been shown to inhibit multiple tyrosine kinases, including potent inhibition of kinases, MET and VEGFR2. Therefore, the goal of this study is to see if Cabozantinib can be used to inhibit MET and VEGFR2, or other tyrosine kinases to drive tumor responses in patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: CabozantinibCabozantinib |
Who may qualify
- Ages
- 5 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (26 listed)
- Histologic diagnosis of any sarcoma, including bone and soft tissue sarcomas. Biopsy from current relapse/progression is highly preferred, though will accept tissue from prior relapse/progression or initial diagnosis with approval from the study Principal Investigator or designee.
- Disease that has progressed on or relapsed after upfront initial therapy, which must have included traditional chemotherapy.
- Evaluable or Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1), within 21 days of enrollment.
- Age, within the following parameters by cohort:
- Body surface area (BSA): > 0.35 m2.
Key exclusion criteria (41 listed)
- Radiographic evidence of tumor invading major blood vessels, or endotracheal or endobronchial tumor.
- Radiographic evidence of tumor invading the gastrointestinal tract, including esophagus, stomach, small or large bowel, rectum, or anus.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy or surgery (including radiosurgery) and stable for at least 4 weeks prior to enrollment after radiotherapy or major surgery (i.e. removal or biopsy of brain metastasis). Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
- Prior progression/relapse with cabozantinib. Prior therapy with cabozantinib without progression/relapse and prior use of other multi-tyrosine kinase inhibitors is allowed.
- Prior therapy with high-dose ifosfamide (> 10 g/m2/cycle) at any point.
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 |
|---|---|---|
| CabozantinibParticipants will receive cabozantinib in combination with high-dose ifosfamide for 5 cycles. If still on study therapy the participants will continue with cabozantinib monotherapy for up to 12 total cycles. | Drug | Treatment |
Primary outcome
Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of cabozantinib
Time frame: Upon completion of accrual to phase 1 cohort, approximately 1 year
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0).
5 secondary outcomes
Toxicity profile
Time frame: Upon completion of trial, approximately 1 year
Dose-limiting toxicities (DLT)
Time frame: After two cycles of treatment, average 56 days (one cycle is 28 days)
Antitumor activity Ewing sarcoma
Time frame: 6 months
Antitumor activity osteosarcoma
Time frame: 6 months
Antitumor Activity Relapsed/Refractory Sarcomas
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Individual participant dataSharing planned: Yes. Children's Hospital of Philadelphia, as the sponsor and lead site for this trial, will have access to all participant data throughout the study. Certain biological samples will be sent to the University of Colorado for processing and analysis.
Related trials for Ewing Sarcoma
RecruitingPhase 1/2
Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)
B-cell Acute Lymphoblastic Leukemia, Diffuse Large B-cell Lymphoma
Not yet recruitingPhase 1/2
Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas
Sarcoma, Osteoid Sarcoma
Not yet recruiting
my.naviGATE: A Guide to After-Treatment Effects for Adolescents and Young Adults
Sarcoma, Osteosarcoma
RecruitingPhase 1
Evaluation of Xaluritamig in Adults, Adolescents and Children With Relapsed or Refractory Ewing Sarcoma (EWS)
Ewing Sarcoma
RecruitingPhase 1
International Phase I Trial of Dinutuximab Beta With VDC/IE in GD2-Positive Ewing Sarkoma
High-risk GD2 Positive Ewing Sarkoma
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.
Theodore Laetsch, MD principal investigator
Children's Hospital of Philadelphia
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cabozantinib in people with Ewing Sarcoma and Osteosarcoma, run by Children's Hospital of Philadelphia at 4 sites in United States.
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 26 inclusion and 41 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: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meghan Donnelly, MPH (267-426-9343, 22ST012@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of cabozantinib (time frame: Upon completion of accrual to phase 1 cohort, approximately 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Sep 2026.