What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma (STS) include chemotherapy agents like doxorubicin and ifosfamide, as well as targeted therapies like cabozantinib. Chemotherapy agents often cause side effects such as myelosuppression, alopecia, mucosal inflammation, and cardiotoxicity. Targeted therapies like cabozantinib, which inhibit multiple kinases, can lead to hypertension, diarrhea, fatigue, palmar-plantar erythrodysaesthesia, and liver enzyme abnormalities. These treatments aim to manage tumor growth but come with significant toxicities that need to be carefully managed.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Soft Tissue Sarcoma (STS). Pazopanib, a tyrosine kinase inhibitor, is approved for advanced STS (excluding adipocytic tumors and GIST) after prior chemotherapy. Regorafenib, another TKI, has shown efficacy in nonadipocytic STS subtypes. These drugs, like cabozantinib, work by inhibiting specific enzymes involved in tumor growth and angiogenesis. Other approved treatments include eribulin for liposarcoma and leiomyosarcoma, and trabectedin for specific subtypes of STS.

What other types of research exist?

Promising alternatives to Cabozantinib for STS patients include Pazopanib, which has shown activity in various STS subtypes and improved progression-free survival in clinical trials. Trabectedin is another option, particularly effective in leiomyosarcoma and liposarcoma. Regorafenib has also demonstrated efficacy in non-adipocytic STS subtypes. These alternatives offer different mechanisms of action and have been validated in recent clinical studies.

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Tyrosine Kinase Inhibitor

Cabozantinib + Radiation Therapy for Soft Tissue Sarcoma

Phase 1 & 2

Waitlist Available

Led By Lee Cranmer

Research Sponsored by University of Washington

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Serum creatinine =< 2.0 x ULN or calculated creatinine clearance >= 30 mL/min (>= 0.5 mL/sec) using the Cockcroft-Gault equation

Subjects whose bowel cannot be completely protected from radiation exposure due to primary tumor location (e.g., proximal lower extremity) will be excluded

Must not have

Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) for the investigational diagnosis

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well cabozantinib, a drug that blocks enzymes needed for cancer cell growth, works with radiation therapy in patients with sarcoma of the extremities. The goal is to see if this combination can make tumors smaller and reduce the need to remove normal tissue. Cabozantinib is a tyrosine kinase inhibitor approved for treating several cancers and has shown promising activity in sarcomas.

Who is the study for?

Adults with confirmed sarcomas of the extremities needing radiation and surgery can join. They must have measurable tumors, proper organ function, no recent serious illnesses or surgeries, not be pregnant or breastfeeding, and agree to contraception. Excluded are those who've had certain treatments for their cancer, have brain metastases or significant heart issues.

What is being tested?

The trial is testing how well cabozantinib works alongside radiation therapy in treating limb sarcomas. It aims to find the best dose with manageable side effects and see if it can shrink tumors effectively before surgical removal.

What are the potential side effects?

Cabozantinib may cause fatigue, high blood pressure, hand-foot skin reactions, gastrointestinal symptoms like diarrhea and nausea, weight loss, decreased appetite and possible liver enzyme changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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My cancer's location means my bowel can be shielded during radiation.

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My platelet count is above 100,000 without recent transfusions.

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My white blood cell count is healthy without needing medication in the last month.

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I will not have unprotected sex with a pregnant woman or a woman who could become pregnant while in the study.

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I am 18 or older with a confirmed sarcoma diagnosis in my limbs or glutes, planning for radiation and surgery.

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I am fully active or can carry out light work.

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My doctors believe my tumor can be removed with surgery.

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My hemoglobin level is at least 9 g/dL without recent transfusions.

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I am a man or a woman not pregnant or breastfeeding.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not received any systemic anticancer treatments for my current cancer diagnosis.

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I do not have any serious uncontrolled health issues, including heart problems or recent strokes.

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My cancer has spread to my brain.

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I do not have serious GI issues, recent significant bleeding, or lung problems that could worsen with treatment.

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I have not received radiation for this specific cancer diagnosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Incidence of adverse events

Response rate (complete, partial, overall)

Side effects data

From 2019 Phase 2 trial • 13 Patients • NCT02315430

85%

Fatigue

77%

Nausea

62%

Dysgeusia

62%

Vomiting

54%

Alkaline Phosphatase Increased

54%

Aspartate Aminotransferase Increased

54%

Mucositis Oral

54%

Abdominal Pain

46%

Hypertension

46%

Anorexia

38%

Alanine Aminotransferase Increased

38%

Thromboembolic Event

38%

Anemia

38%

Diarrhea

38%

Constipation

38%

Cough

38%

Weight Loss

38%

Dyspnea

31%

Hypomagnesemia

31%

Back Pain

31%

Lipase Increased

31%

Hypoalbuminemia

23%

Hypophosphatemia

23%

Hyperglycemia

23%

Dizziness

23%

Palmar-Plantar Erythrodysesthesia Syndrome

23%

Alopecia

23%

Hypothyroidism

23%

Pain In Extremity

23%

Oral Pain

23%

Pain

23%

Headache

15%

Sore Throat

15%

Activated Partial Thromboplastin Time Prolonged

15%

Myalgia

15%

Bloating

15%

White Blood Cell Decreased

15%

Insomnia

15%

Dry Mouth

15%

Dyspepsia

15%

Dehydration

15%

Hypocalcemia

15%

Dry Skin

15%

Flushing

15%

Peripheral Sensory Neuropathy

15%

Abdominal Distension

15%

Platelet Count Decreased

Allergic Rhinitis

Generalized Muscle Weakness

Creatinine Increased

Hyponatremia

Flank Pain

Bone Pain

Gastroesophageal Reflux Disease

Chest Pain - Cardiac

Vertigo

Neutrophil Count Decreased

Arthralgia

Syncope

Proteinuria

Pleural Effusion

Nasal Congestion

Pleuritic Pain

Hoarseness

Nail Discoloration

Ventricular Tachycardia

Tinnitus

Gastrointestinal Pain

Floaters

Dysphagia

Blood Bilirubin Increased

Lung Infection

Fever

Depression

Hypersomnia

Hypotension

Productive Cough

Memory Impairment

Anxiety

Cardiac Troponin I Increased

Urinary Incontinence

Pancreatitis

Upper Respiratory Infection

Bruising

Weight Gain

Skin Induration

100%

80%

60%

40%

20%

Study treatment Arm

Cabozantinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (cabozantinib S-malate, radiation therapy)Experimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cabozantinib S-malate

2013

Completed Phase 2

~490

Radiation Therapy

2017

Completed Phase 3

~7250

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Soft Tissue Sarcoma (STS) include chemotherapy, targeted therapy, and enzyme inhibitors like cabozantinib. Chemotherapy works by killing rapidly dividing cells, which includes cancer cells, but can also affect normal cells, leading to side effects. Targeted therapies, such as tyrosine kinase inhibitors, specifically block molecules involved in cancer cell growth and survival. Cabozantinib, an enzyme inhibitor, targets multiple pathways including MET and VEGFR, which are crucial for tumor growth and angiogenesis. By inhibiting these pathways, cabozantinib can reduce tumor size and limit cancer spread. This is particularly important for STS patients as it offers a more focused treatment approach, potentially with fewer side effects compared to traditional chemotherapy, and can be effective in cases where other treatments have failed.

Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group.Cabozantinib and dastinib exert anti-tumor activity in alveolar soft part sarcoma.Fifty years of advances in sarcoma treatment: moving the needle from conventional chemotherapy to targeted therapy.