What is the mechanism of action of this treatment?

The most common treatments for Angiomatoid Fibrous Histiocytoma (AFH) often involve tyrosine kinase inhibitors (TKIs) like Pazopanib, which block enzymes necessary for cell growth. Pazopanib targets multiple receptors such as VEGFR, PDGFR, and c-Kit, which are involved in tumor growth and angiogenesis. By inhibiting these pathways, Pazopanib can reduce tumor vascularization and proliferation. This is crucial for AFH patients as it directly targets the molecular mechanisms driving tumor growth, potentially leading to more effective treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for Angiomatoid Fibrous Histiocytoma, particularly those similar to Pazopanib, which blocks enzymes needed for cell growth, often involve tyrosine kinase inhibitors (TKIs). These treatments are associated with side effects such as hypertension, diarrhea, hair color changes, nausea, fatigue, and liver function abnormalities. More severe side effects can include hepatotoxicity, cardiac dysfunction, and gastrointestinal perforations.

What prior FDA approvals exist?

There is no specific mention of FDA approvals for the treatment of Angiomatoid Fibrous Histiocytoma (AFH) in the provided context. However, drugs like Pazopanib, which block enzymes needed for cell growth, are being studied for their efficacy in treating various types of soft tissue sarcomas. Pazopanib is approved for the treatment of advanced soft tissue sarcomas (excluding adipocytic tumors and GIST) after prior chemotherapy. Other similar drugs that target angiogenesis and have been evaluated in soft tissue sarcomas include sunitinib, sorafenib, and regorafenib.

What other types of research exist?

Promising alternatives to Pazopanib for treating Angiomatoid Fibrous Histiocytoma in 2024 include Regorafenib and Cabozantinib. Both are tyrosine kinase inhibitors that have shown efficacy in treating various sarcomas by targeting multiple pathways involved in tumor growth and angiogenesis.

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Anthracyclines

Chemotherapy + Radiation for Soft Tissue Sarcoma

Phase 2 & 3

Waitlist Available

Led By Aaron R Weiss

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma not otherwise specified [NOS]")

Patient must have a life expectancy of at least 3 months with appropriate therapy

Must not have

Patients with evidence of active bleeding or bleeding diathesis

Patients with gross total resection of the primary tumor prior to enrollment on ARST1321

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from enrollment up to 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether a new drug called pazopanib, when combined with chemotherapy and radiation, works better for patients with a specific type of soft tissue cancer. Pazopanib helps stop cancer cells from growing, while chemotherapy and radiation kill the cells. The goal is to see if this combination can improve treatment outcomes.

Who is the study for?

This trial is for patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can be surgically removed. Eligible participants include those with various types of sarcoma, adequate organ function, and no metastases to the central nervous system. They must be able to swallow tablets, have a life expectancy of at least 3 months, and not have received certain prior treatments.

What is being tested?

The study is testing whether pazopanib combined with chemotherapy (ifosfamide and doxorubicin) and radiation therapy works better than radiation alone in treating these sarcomas before surgery. Pazopanib blocks enzymes needed for tumor growth while chemotherapy kills or stops cancer cells from dividing.

What are the potential side effects?

Potential side effects may include fatigue, nausea, hair loss from chemotherapy; high blood pressure, liver changes from pazopanib; skin irritation from radiation; plus risks associated with surgery such as infection or bleeding.

Eligibility Criteria

Inclusion Criteria

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

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My sarcoma is not classified under specific types.

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My doctor expects me to live at least 3 more months with treatment.

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My initial cancer cannot be surgically removed, but there's a plan to operate on the main tumor.

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My cancer is larger than 5 cm but hasn't spread widely, and is moderately to poorly differentiated.

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I can swallow pills and my body size is suitable for the treatment.

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My bilirubin levels are within normal range for my age.

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My liver enzymes are within normal limits for my age.

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I am over 16 and can care for myself but may not be able to do active work.

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My kidney function is normal or near normal.

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I am 16 or younger and can do most activities without help.

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I have a new, operable soft tissue sarcoma in my limb or trunk.

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My diagnosis was confirmed with a biopsy, not just a fine needle aspiration.

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I can swallow pills and my body surface area is at least 0.5 m^2.

Exclusion Criteria

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

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I do not have any current bleeding or conditions that cause excessive bleeding.

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I had surgery to completely remove my tumor before joining ARST1321.

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My high blood pressure is not under control.

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I am not taking any strong CYP3A4 inhibitors.

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I have previously received anthracycline or ifosfamide chemotherapy.

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I have previously used pazopanib or similar cancer drugs.

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I cannot swallow whole tablets.

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My body surface area is less than 0.5 square meters.

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I am HIV-positive and on combination antiretroviral therapy.

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I am a woman able to have children and do not plan to use birth control.

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I do not have any unmanaged ongoing illnesses.

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My tumor is grade 1 and can be any size.

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I am not taking any medications that are sensitive to changes in how they are broken down by the body.

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My cancer has spread to my brain.

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I have had radiation therapy on the cancer-affected areas.

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I am not taking any medications that speed up drug breakdown.

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I have not had serious heart problems in the last 6 months.

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I have a serious or non-healing wound, ulcer, or bone fracture.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from enrollment up to 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from enrollment up to 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from enrollment up to 60 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Feasible Dose: Adult

Feasible Dose: Pediatric

Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13

+2 more

Secondary study objectives

Percentage of Patients Distant Failure Free at 5 Years Following Study Entry

Percentage of Patients Local Failure Free at 5 Years Following Study Entry

Percentage of Patients Regional Failure Free at 5 Years Following Study Entry

+1 more

Other study objectives

Change in Fludeoxyglucose F 18 (FDG) Positron Emission Tomography (PET) Maximum Standard Uptake Value (SUVmax)

Mean Pharmacokinetic Parameters of Doxorubicin and Pazopanib

Prevalence of Circulating Tumor DNA (ctDNA)

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Regimen D (radiation therapy)Experimental Treatment2 Interventions

INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.

Group II: Regimen C (pazopanib, radiation therapy)Experimental Treatment4 Interventions

INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.

Group III: Regimen B (chemoradiation)Experimental Treatment5 Interventions

See Regimen B Detailed Description.

Group IV: Regimen A (pazopanib, chemoradiation)Experimental Treatment7 Interventions

See Regimen A Detailed Description.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Doxorubicin Hydrochloride

2019

Completed Phase 3

~17860

Ifosfamide

2010

Completed Phase 4

~3350

Doxorubicin

2012

Completed Phase 3

~8030

Pazopanib Hydrochloride

2009

Completed Phase 2

~820

Pazopanib

2012

Completed Phase 4

~1700

Radiation Therapy

2017

Completed Phase 3

~7250

Therapeutic Conventional Surgery

2005

Completed Phase 3

~9890

0 / 31Eligibility 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 Angiomatoid Fibrous Histiocytoma (AFH) often involve tyrosine kinase inhibitors (TKIs) like Pazopanib, which block enzymes necessary for cell growth. Pazopanib targets multiple receptors such as VEGFR, PDGFR, and c-Kit, which are involved in tumor growth and angiogenesis. By inhibiting these pathways, Pazopanib can reduce tumor vascularization and proliferation. This is crucial for AFH patients as it directly targets the molecular mechanisms driving tumor growth, potentially leading to more effective treatment outcomes.

Outcome of uterine sarcoma patients treated with pazopanib: A retrospective analysis based on two European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) clinical trials 62043 and 62072.