Last updated on July 2020

MDM2 Inhibitor AMG-232 (KRT-232) and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma

Brief description of study

This phase Ib trial studies the side effects of MDM2 inhibitor AMG-232 (KRT-232) and radiation therapy in treating patients with soft tissue sarcoma. MDM2 inhibitor AMG-232 (KRT-232) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving MDM2 inhibitor AMG-232 (KRT-232) and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Study Description


I. To evaluate the safety and tolerability of MDM2 inhibitor KRT-232 (AMG-232 [KRT-232]) in combination with standard-dose radiotherapy in soft tissue sarcoma (STS) in two separate patient cohorts (A, extremity or body wall; B, abdomen/pelvis/retroperitoneum).

II. To determine the maximum tolerated dose/recommended phase II dose (maximum tolerated dose/recommended phase 2 dosage [MTD/RP2D]) of AMG 232 (KRT-232) in combination with radiotherapy.


I. To observe and record anti-tumor activity. II. To determine % necrosis and pathologic complete response (pCR) in final surgical resection specimen.

III. To determine % local failure (LF), disease free survival (DFS) and overall survival (OS) at 2 years.

IV. To determine pharmacodynamics (PD) effects of AMG 232 (KRT-232) when combined with radiotherapy by assessing serial serum macrophage inhibitory cytokine (MIC)-1 levels.

V. To determine AMG 232 (KRT-232) exposure (pharmacokinetics)-response relationships (PD, toxicity, and efficacy).


I. To determine tumor volume changes determined by magnetic resonance imaging (MRI) or computed tomography (CT) with and without contrast pre- and post-radiotherapy.

II. To characterize clinical outcomes in patients treated with AMG 232 (KRT-232) by genomic biomarkers.

III. To determine the correlation between mdm2/4 expression determined by next-generation sequencing (NGS) and the protein levels by immunohistochemistry (IHC).

IV. To explore the possibility of identifying tumor genetic mutations in (1) cell-free (cf) circulating tumor deoxyribonucleic acid (ctDNA), (2) deoxyribonucleic acid/ribonucleic acid (DNA/RNA) isolated from exosomes, and determine the concordance of these results and that from NGS.

OUTLINE: This is a dose escalation study.

Patients receive MDM2 inhibitor KRT-232 orally (PO) on day 2, days 2 and 4, days 2-4, days 2-5, or days 1-5 of weeks 1 to 5. Patients also undergo radiation therapy daily on weeks 1-5. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, and then at 2.5 years.

Clinical Study Identifier: NCT03217266

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Northwestern University

Chicago, IL United States
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Eastern Regional Medical Center

Philadelphia, PA United States
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Aurora Health Center-Fond du Lac

Fond Du Lac, WI United States
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Aurora Cancer Care-Grafton

Grafton, WI United States
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Aurora BayCare Medical Center

Green Bay, WI United States
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Aurora Cancer Care-Milwaukee

Milwaukee, WI United States
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Aurora Sinai Medical Center

Milwaukee, WI United States
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Aurora Cancer Care-Racine

Racine, WI United States
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Northside Hospital

Atlanta, GA United States
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Recruitment Status: Open

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