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New treatment option for Ewing Sarcoma
Official title Cabozantinib With Ifosfamide in Relapsed/Refractory Sarcomas
ClinicalTrials.gov ID: NCT06156410
What this study is testing
What is Cabozantinib?
Cabozantinib is an investigational medicine, being studied as a potential treatment for ewing sarcoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 5 to 40
You may be able to join if
- Histologic diagnosis of any sarcoma, including bone and soft tissue sarcomas. Biopsy from current relapse/progression is highly preferred, though...
- 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.
You likely can't join if
- 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...
- Prior progression/relapse with cabozantinib. Prior therapy with cabozantinib without progression/relapse and prior use of other multi-tyrosine kinase...
- 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.
See the full eligibility criteria
Who can 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...
- 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.
- Body surface area (BSA): \> 0.35 m2.
- Performance status: Lansky play (\ 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...
- 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 \ 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 people 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...
- Serum albumin \> 2.8 g/dL.
- Prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.3 x ULN.
- Sexually active fertile people 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...
- Female people of childbearing potential must not be pregnant at screening. Female people 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...
What rules you out
- 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...
- 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.
- 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. people with any clinically...
- 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...
- 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...
- 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 people without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before...
- 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 people and \> 140/90 mmHg for adult people, 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...
- 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...
- 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.
The study team makes the final eligibility decision.
Where it's taking place
- San Francisco, California, United States
- Aurora, Colorado, United States
- Philadelphia, Pennsylvania, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 5 years to 40 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include San Francisco, California, United States; Aurora, Colorado, United States; Philadelphia, Pennsylvania, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.