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

NCT04220229 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: RG1003562NCI-2019-0866110051
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Soft Tissue

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose of Cabozantinib S-malate (Cabozantinib) (Phase I)

  Cabozantinib treatment begins 8 days prior to initiation of radiation therapy and continues through completion of radiation therapy.

  Up to 21 days

• Rate of Relapse (Phase II)

  No patients were enrolled in Phase II portion of study - outcome measure based on Phase I patients.

  At 12 months after treatment initiation

Secondary Outcomes (9)

• Rate of Pathologic Response(>90%)

  Up to 1 year

• Rate of Surgical Excision With Negative Margins

  Up to 1 year

• Objective Response Rate

  Up to 1 year

• Rate of Local Relapse

  Up to 3 years

• Rate of Distant Relapse

  Up to 3 years

Study Arms (1)

Treatment (cabozantinib S-malate, radiation therapy)

EXPERIMENTAL

Patients receive cabozantinib S-malate PO 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 1 day 8, patients also undergo standard of care radiation therapy for 5-6 weeks.

Drug: Cabozantinib S-malate; Radiation: Radiation Therapy

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: 1140909-48-3, BMS-907351, Butanedioic acid, Cabometyx, Cometriq

Treatment (cabozantinib S-malate, radiation therapy)

Radiation Therapy RADIATION

Undergo standard of care radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, irradiated, Irradiation, RADIATION, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (cabozantinib S-malate, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects, \>= 18 years old, 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)

You may not qualify if:

• 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
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
• 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

Sponsors & Collaborators

• University of Washington: lead
• Exelixis: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

  PMID: 32827353 DERIVED

MeSH Terms

Interventions

cabozantinib; Succinic Acid; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Lee Cranmer, MD, PhD
• Organization: City of Hope

lcranmer@coh.org

626-256-4673

Study Officials

• Lee Cranmer, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 7, 2020
• Study Start: June 1, 2020
• Primary Completion: April 5, 2024
• Study Completion: October 31, 2024
• Last Updated: July 17, 2025
• Results First Posted: July 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)