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

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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).

EXPLORATORY OBJECTIVES:

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

Find a site near you

Start Over

Northwestern University

Chicago, IL United States
  Connect »

Eastern Regional Medical Center

Philadelphia, PA United States
  Connect »

Aurora Health Center-Fond du Lac

Fond Du Lac, WI United States
  Connect »

Aurora Cancer Care-Grafton

Grafton, WI United States
  Connect »

Aurora BayCare Medical Center

Green Bay, WI United States
  Connect »

Aurora Cancer Care-Milwaukee

Milwaukee, WI United States
  Connect »

Aurora Sinai Medical Center

Milwaukee, WI United States
  Connect »

Aurora Cancer Care-Racine

Racine, WI United States
  Connect »

Northside Hospital

Atlanta, GA United States
  Connect »

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


Volunteer Sign-up

Sign up for our FREE service to receive email notifications when clinical trials are posted in the medical category of interest to you.