Cabozantinib With Radiation Therapy for the Treatment of Sarcomas of the Extremities

  • End date
    Jan 1, 2026
  • participants needed
  • sponsor
    University of Washington
Updated on 4 October 2022


This phase I/II trial studies the side effects and best dose of cabozantinib when given with radiation therapy and how well it works in treating patients with sarcoma of the extremities. Cabozantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cabozantinib with radiation therapy may make the tumors smaller and reduce the amount of normal tissue that needs to be removed.


OUTLINE: This is a phase I, dose-escalation study of cabozantinib followed by a phase II, dose-expansion study.

Patients receive cabozantinib S-malate orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days until the completion of radiation therapy in the absence of disease progression or unacceptable toxicity. Beginning cycle 2, patients also undergo standard of care radiation therapy for 5-6 weeks.

After completion of study treatment, patients are followed up at 30 days, every 12 weeks for up to 1 year, then every 6 months for up to 3 years.

Condition Sarcoma of the Extremity, Stage I Soft Tissue Sarcoma of the Trunk and Extremities, Stage IA Soft Tissue Sarcoma of the Trunk and Extremities, Stage IB Soft Tissue Sarcoma of the Trunk and Extremities, Stage II Soft Tissue Sarcoma of the Trunk and Extremities
Treatment radiation therapy, Cabozantinib, Cabozantinib S-malate
Clinical Study IdentifierNCT04220229
SponsorUniversity of Washington
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

Subjects must have a histologically confirmed diagnosis of sarcomas of the extremities (which may include gluteal muscle involvement) for which neoadjuvant radiation therapy followed by surgical resection is a planned intervention
Subjects whose bowel cannot be completely protected from radiation exposure due to primary tumor location (e.g., proximal lower extremity) will be excluded
Subjects must have one or more measurable target lesions by RECIST version (v) 1.1
assessed via computed tomography (CT) scan or magnetic resonance imaging (MRI)
At the time of study enrollment, subjects must have a tumor burden that is judged to be surgically resectable
Absolute neutrophil count (ANC) >= 1500/mm^3 (>= 1.5 GI/L) without granulocyte colony-stimulating factor support in the last 28 days
White blood cell count >= 2500/mm^3 (>= 2.5 GI/L)
Platelets >= 100,000/mm^3 (>=100 GI/L) without transfusion in the last 28 days
Hemoglobin >= 9 g/dL (>= 90 g/L) without transfusion in the last 28 days
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =< 3 X upper limit of normal (ULN)
Alkaline phosphatase (ALP) =< 3 X upper limit of normal (ULN)
ALP =< 5 X ULN is permitted in subjects with documented bone metastases (phase 1 only)
Total bilirubin =< 1.5 x ULN (for subjects with Gilbert's disease =< 3 X ULN)
Serum albumin >= 2.8 g/dl
Serum creatinine =< 2.0 x ULN or calculated creatinine clearance >= 30 mL/min (>= 0.5 mL/sec) using the Cockcroft-Gault equation
Urine protein/creatinine ratio (UPCR) =< 1 mg/mg (=< 113.2 mg/mmol)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Male or non-pregnant and non-breast feeding female
Females of child-bearing potential must agree to use highly effective contraception without interruption from initiation of therapy and while on study medication and have a negative serum pregnancy test (beta-human chorionic gonadotropin [B-hCG]) result at screening and agree to ongoing pregnancy testing during the study, and at the end of study treatment. A highly effective method of contraception is defined as one that results in a low failure rate (that is, < 1% per year), when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner
Male subjects must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study
Life expectancy of > 3 months, as determined by the investigator
Ability to understand and sign informed consent
Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures
Resolution to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) 5.0 for any toxicities related to any prior treatment (except alopecia)

Exclusion Criteria

Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) for the investigational diagnosis
Receipt of any prior radiation therapy for the investigational diagnosis
Known central nervous system (CNS) metastases
Concomitant anticoagulation with oral anticoagulants(e.g., warfarin, direct thrombin and factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following
Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted
Low-dose low molecular weight heparins (LMWH) are permitted
Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor. Subjects with hemoptysis, central nervous system hemorrhage or gastrointestinal hemorrhage within the last 6 months prior to treatment are excluded
Cardiovascular disorders
The subject has uncontrolled, significant intercurrent or recent illness including
Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
but not limited to, the following conditions
Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal anti-hypertensive treatment
Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose
Uncontrolled serious medical or psychiatric illness
Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation
The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose
Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose
Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon
Lesions invading or encasing any major blood vessels
(2.5 ml) of red blood, or other history of significant bleeding (e.g
Other clinically significant disorders that would preclude safe study participation
pulmonary hemorrhage) within 12 weeks before first dose
Serious non-healing wound/ulcer/bone fracture
Uncompensated/symptomatic hypothyroidism
Moderate to severe hepatic impairment (Child-Pugh B or C)
Corrected QT interval calculated by the Bazett's formula (corrected QT [QTc]) > 480 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment
Note: If a single ECG shows a QTc with an absolute value > 480 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTc will be used to determine eligibility
Pregnant or lactating females
Inability to swallow tablets
Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks
Previously identified allergy or hypersensitivity to components of the study treatment formulations
before first dose of study treatment. Complete wound healing from major
surgery must have occurred 1 month before first dose and from minor surgery
Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy
(e.g., simple excision, tooth extraction) at least 10 days before first dose
Concurrent use of medications (especially those interacting with CYP3A417) that potentially interact unsafely with cabozantinib which cannot be discontinued or substituted
Subjects with clinically relevant ongoing complications from prior surgery are
Subjects with a sarcoma which has other, defined treatments or biology distinctly different from those of soft tissue sarcomas in general. Including, but not limited to, Ewing's sarcoma, rhabdomyosarcoma, gastrointestinal stromal tumors, Kaposi's sarcoma, Wilms' tumor
Transfusion of blood product or granulocyte-colony stimulating factor (G-CSF) support factor within the last 28 days
not eligible
Recent infection requiring systemic anti-infective treatment that was completed =< 14 days prior to enrollment (except for uncomplicated urinary tract infection or upper respiratory tract infection)
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