Experimental combo shrinks sarcomas before surgery?

NCT ID NCT03217266

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 24, 2026 · Last updated Jun 26, 2026 · Updated 2 times

Summary

This early-phase trial tested a drug called navtemadlin given alongside radiation therapy before surgery for soft tissue sarcoma. The goal was to find a safe dose and see if the combination could shrink tumors, making surgery easier. 39 patients with intermediate or high-grade sarcomas at least 5 cm in size took part. The study focused on safety and side effects, not on curing the cancer.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Navtemadlin (also called AMG 232 or KRT-232)
What this could lead to: If it works, this could point toward a new way to shrink soft tissue sarcomas before surgery, potentially reducing the amount of tissue that needs to be removed.
What could go wrong: This is a very early phase 1 trial with only 39 participants, focused on safety and dosing. It is not designed to prove effectiveness, and side effects may be severe.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

39 people

The number who actually took part.

Started

Jun 2018

Finished

Sep 2025

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA * Patients with pathologically proven diagnosis of grade 2-3 (intermediate or high grade) soft tissue sarcoma with size \>= 5 cm are eligible to enroll if the intention to treat is curative. They must have sufficient tissue to submit to central laboratory for review as well as for NGS sequencing (see submission requirement). Biopsy should be obtained within 180 days prior to registration. Availability of tumor tissue is mandatory for study eligibility. The patient must have consented to provide archived formalin-fixed paraffin-embedded tumor tissue for future central pathology review, NGS sequencing and/or translational research * Appropriate stage for study entry based on the following diagnostic workup: * History/physical examination within 30 days prior to registration; * Imaging of the primary tumor by MRI and/or computed tomography (CT) with or without contrast and/or positron emission tomography (PET)/CT within 30 days prior to registration; * Staging workup evaluated by chest CT and/or PET/CT showing no distant metastasis within 30 days prior to registration * There is a planned definitive surgical resection of the primary tumor * Eastern Cooperative Oncology Group (ECOG) or Zubrod performance status of 0-1 within 30 days prior to registration * Absolute neutrophil count \>= 1500/uL (within 30 days prior to registration) * Platelet count \>= 100,000/uL (within 30 days prior to registration) * Hemoglobin: \>= 10 g/dL (transfuse as necessary to raise levels; no transfusions within 7 days of start) (within 30 days prior to registration) * Calculated creatinine clearance \>= 60 ml/min (by Cockcroft-Gault formula) within 30 days prior to registration * The patient has an adequate coagulation function as defined by international normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN) or prothrombin time (PT) =\< 1.5 x ULN, and partial thromboplastin time (PTT or aPTT) =\< 1.5 x ULN (those receiving anticoagulation therapy except low molecular weight heparin are excluded) (within 30 days prior to registration) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) appropriate for age (except for patients with Gilbert's syndrome, who must have a total bilirubin \< 3 mg/dL) (within 30 days prior to registration) * Serum glutamic-oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT) alanine aminotransaminase (ALT) \< 2.5 upper limit of normal (ULN) appropriate for age (within 30 days prior to registration) * Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to registration; exceptions: females not of child-bearing potential due to surgical sterilization (at least 6 weeks following tubal ligation, hysterectomy, or surgical bilateral oophorectomy with or without hysterectomy) confirmed by medical history; or female after menopause * A "postmenopausal woman" is a woman meeting either of the following criteria: * Spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example, oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators \[SERMs\], or chemotherapy) * Spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone (FSH) level \> 40 mIU/mL * Females of child-bearing potential and males must agree to use highly effective contraceptive precautions during the trial and up to 12 months following the last dose of study treatment; a highly effective method of birth control is defined as one that results in a low failure rate (that is, \< 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry * PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA * TP53 sequencing by NGS performed by central pathology lab Exclusion Criteria: * PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA * Well-differentiated liposarcoma or other low grade STS; Kaposi sarcoma, bone sarcomas, cartilage sarcomas and gastrointestinal stromal tumor (GIST) * Definitive clinical or radiologic evidence of metastatic disease; indeterminant lung nodules less than 8 mm are acceptable * The patient has history of another primary malignancy, with the exception of * Curatively treated non-melanomatous skin cancer; * Curatively treated cervical carcinoma in situ; * Non-metastatic prostate cancer * Other primary non-hematologic malignancies or solid tumor treated with curative intent, no known active disease, and no treatment administered during the last 3 years prior to registration * The patient has a serious cardiac condition, such as congestive heart failure; New York Heart Association class II/ III/IV heart disease; unstable angina pectoris, cardiac stenting within 6 months of enrollment; myocardial infarction within the last 3 months; valvulopathy that is severe, moderate, or deemed clinically significant; or arrhythmias that are symptomatic or require treatment * Females who are pregnant or breastfeeding * Prior systemic chemotherapy for the study cancer (sarcoma); note that prior chemotherapy for a different cancer is allowable; however, unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible \[defined as having been present and stable for \> 6 months\], such as ifosfamide-related proteinuria, may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor) * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields * Clinically significant bleeding within 4 weeks of screening, current use of warfarin, factor Xa inhibitors, and direct thrombin inhibitors unless these medications can be safely discontinued 14 days prior to AMG-232 (KRT-232) administration; Note: low molecular weight heparin and prophylactic low dose warfarin are permitted; PT/PTT must meet the inclusion criteria; subjects taking warfarin must have their INR followed closely * History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 232 (KRT-232) * All subjects must agree to stop the use of all herbal medicines (e.g., St. John's wort), and supplements, within the 10 days prior to receiving the first dose of AMG 232 (KRT-232), and during the protocol AMG 232 (KRT-232) treatment (weeks 1-5); subjects may renew the use of the above at week 6; standard adult multi-vitamin is allowed * All subjects must agree to stop the use of any known CYP3A4 substrates with narrow therapeutic window (such as alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, sirolimus, or terfenadine; within the 14 days prior to receiving the first dose of AMG 232 (KRT-232) and during protocol AMG 232 (KRT-232) treatment (weeks 1-5); other medications (such as fentanyl and oxycodone) may be allowed per investigator's assessment/evaluation * All subjects must agree to stop the use of any known CYP2C8 substrates with a narrow therapeutic window within the 14 days prior to receiving the first dose of AMG 232 (KRT-232) and during protocol AMG 232 (KRT-232) treatment (weeks 1-5) * All subjects are required to submit a list of medications consumed within 14 days prior to receiving the first dose of AMG232 (KRT-232) and during the protocol AMG232 (KRT-232) treatment (weeks 1-5) * Patients with gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis), therefore could affect the absorption of AMG 232 (KRT-232) at the discretion of treating physician * Patients with active infection requiring intravenous (IV) antibiotics within 2 weeks of registration * Patients with known positive hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B), positive hepatitis total core antibody with negative HBsAG (suggestive of occult hepatitis B), or detectable hepatitis C virus RNA by a polymerase-chain reaction (PCR) assay (indicative of active hepatitis C - screening is generally done by hepatitis C antibody (HepCAb), followed by hepatitis C virus RNA by PCR if HepCAb is positive) * Patients known to be positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have: * A stable regimen of highly active anti-retroviral therapy (HAART) * No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections * A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based test * HIV testing is not required * Treatment with medications known to cause corrected QT (QTc) interval prolongation within 7 days of study day 1 is not permitted unless approved by the sponsor; use of ondansetron is permitted for treatment of nausea and vomiting

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Conditions

The condition(s) this trial relates to.

sarcoma soft tissue sarcoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Resectable soft tissue sarcoma Soft tissue sarcoma

Contacts and locations

Locations

Aurora Bay Area Medical Group-Marinette

Marinette, Wisconsin, 54143, United States
Aurora BayCare Medical Center

Green Bay, Wisconsin, 54311, United States
Aurora Cancer Care-Grafton

Grafton, Wisconsin, 53024, United States
Aurora Cancer Care-Kenosha South

Kenosha, Wisconsin, 53142, United States
Aurora Cancer Care-Milwaukee

Milwaukee, Wisconsin, 53209, United States
Aurora Cancer Care-Milwaukee West

Wauwatosa, Wisconsin, 53226, United States
Aurora Cancer Care-Racine

Racine, Wisconsin, 53406, United States
Aurora Cancer Care-Southern Lakes VLCC

Burlington, Wisconsin, 53105, United States
Aurora Health Care Germantown Health Center

Germantown, Wisconsin, 53022, United States
Aurora Health Center-Fond du Lac

Fond du Lac, Wisconsin, 54937, United States
Aurora Medical Center in Summit

Summit, Wisconsin, 53066, United States
Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States
Aurora Sinai Medical Center

Milwaukee, Wisconsin, 53233, United States
Aurora West Allis Medical Center

West Allis, Wisconsin, 53227, United States
Benefis Sletten Cancer Institute

Great Falls, Montana, 59405, United States
CTCA at Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States
CTCA at Western Regional Medical Center

Goodyear, Arizona, 85338, United States
Eastern Regional Medical Center

Philadelphia, Pennsylvania, 19124, United States
Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States
Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States
Logan Health Medical Center

Kalispell, Montana, 59901, United States
Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States
Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States
Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States
Northside Hospital

Atlanta, Georgia, 30342, United States
Northwestern University

Chicago, Illinois, 60611, United States
Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States
Parkland Memorial Hospital

Dallas, Texas, 75235, United States
Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Rush University Medical Center

Chicago, Illinois, 60612, United States
Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States
Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States
Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States
Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States
The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States
Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States
UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States
UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States
UPMC-Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States
UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States
University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona, 85704, United States
University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States
University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States
University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States
Vince Lombardi Cancer Clinic - Oshkosh

Oshkosh, Wisconsin, 54904, United States
Vince Lombardi Cancer Clinic-Sheboygan

Sheboygan, Wisconsin, 53081, United States
Vince Lombardi Cancer Clinic-Two Rivers

Two Rivers, Wisconsin, 54241, United States
Washington University School of Medicine

St Louis, Missouri, 63110, United States

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