Pembrolizumab and Radiation Therapy With or Without Neoadjuvant Doxorubicin and Ifosfamide for the Treatment of High-Risk Resectable Undifferentiated Pleomorphic Sarcoma or Liposarcoma of the Extremity or Trunk Wall
Comparing Treatment With Versus Without Neoadjuvant Doxorubicin and Ifosfamide in Selected Patients With High-Risk Resectable Soft-Tissue Sarcoma
2 other identifiers
interventional
228
1 country
1
Brief Summary
This phase III trial compares the effect of adding doxorubicin and ifosfamide (AIM chemotherapy) before (neoadjuvant) receiving standard treatment with pembrolizumab, radiation therapy and surgery to standard of care treatment alone in treating patients with high-risk soft-tissue sarcomas, such as undifferentiated pleomorphic sarcoma (UPS) or liposarcoma (LPS), that originate in the arms, legs (extremity) or torso (trunk wall) and can be removed by surgery (resectable). Doxorubicin comes from the bacterium Streptomyces peucetius. It damages deoxyribonucleic acid (DNA) and may kill tumor cells. It is a type of anthracycline antitumor antibiotic. Ifosfamide attaches to DNA in cells and may kill tumor cells. It is a type of alkylating agent and a type of antimetabolite. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Intensity-modulated radiation therapy (IMRT)is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. Giving neoadjuvant doxorubicin and ifosfamide with standard of care pembrolizumab, radiation therapy and surgery may be safe, tolerable, and/or more effective than standard of care therapy alone in treating patients with high-risk resectable soft tissue sarcoma of the arms, legs, or torso.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 11, 2026
CompletedFirst Posted
Study publicly available on registry
September 16, 2026
CompletedStudy Start
First participant enrolled
December 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2028
Study Completion
Last participant's last visit for all outcomes
December 31, 2028
September 16, 2026
September 1, 2026
2.1 years
September 11, 2026
September 11, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Disease-free survival (DFS)
DFS will be estimated using the Kaplan-Meier method and compared between treatment groups using the stratified log-rank test. In addition, a Cox proportional hazards model will be used to estimate the hazard ratio and 95% confidence interval, adjusting for relevant covariates.
From randomization to disease recurrence of death, whichever occurs first, assessed up to 2 years
Secondary Outcomes (5)
Patient-reported quality of life (QOL)
At baseline and at 1 and 2 years post-randomization
Overall survival (OS)
From randomization to death from any cause, assessed up to 5 years
Loco-regional DFS
Up to 5 years
Distant DFS
Up to 5 years
Incidence of treatment-related adverse events (TRAEs)
Up to 5 years
Study Arms (2)
Arm A (AIM, pembrolizumab, IMRT, surgery)
EXPERIMENTALSee Detailed Description
Arm B (pembrolizumab, IMRT, surgery)
ACTIVE COMPARATORNEOADJUVANT: Patients receive standard of care pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 8, patients undergo radiation therapy, patients undergo IMRT QD on Monday-Friday (5 days per week) for up to 25 fractions (5 weeks) per standard of care. Starting 4-6 weeks after completing radiation therapy, patients undergo oncologic resection per standard of care. POST-SURGERY: Starting 1-4 weeks after surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle per standard of care. Cycles repeat every 21 days for up to a total of 17 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo TTE or MUGA at screening, and blood sample collection, CT and MRI throughout the study.
Interventions
Undergo blood sample collection
Undergo CT
Given IV
Given IV
Undergo IMRT
Undergo MRI
Undergo MUGA
Given IV
Ancillary studies
Undergo oncologic resection
Undergo TTE
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Histologically proven diagnosis of UPS or LPS originating in an extremity or trunk wall. Alternative terms for UPS include but are not limited to the following:
- Fibrosarcoma
- Malignant fibrous histiocytoma
- Myxofibrosarcoma
- Pleomorphic fibroblastic sarcoma
- Pleomorphic sarcoma with giant cells
- Pleomorphic sarcoma with prominent inflammation
- Pleomorphic spindle cell sarcoma
- Pleomorphic undifferentiated sarcoma
- Spindle cell sarcoma, not otherwise specified (NOS)
- Unclassified spindle cell sarcoma
- Undifferentiated high-grade pleomorphic sarcoma
- Please contact the medical monitor or study principal investigator (PI) with any questions regarding potentially eligible histologies
- +17 more criteria
You may not qualify if:
- Patients with evidence of nodal metastases or distant metastases (DM)
- Lung nodule(s) between 0.6-1.0 cm are permitted on study if stable on imaging for least 6 months or if fluorodeoxyglucose-positron emission tomography (FDG-PET) scan suggests that the nodule(s) are low-risk for metastatic disease
- Lung nodules \> 1.0 cm should be considered metastatic unless proven otherwise by biopsy or resection or if nodules have stable appearance for at least 6 months on imaging
- Hypersensitivity to DOXOrubicin, ifosfamide, mesna, or pembrolizumab or their metabolites or excipients
- Prior treatment with DOXOrubicin (or other anthracyclines and anthracenediones)
- Clinically significant cardiac disease, including, but not limited to:
- Symptomatic congestive heart failure
- Angina pectoris
- Acute inflammatory heart disease
- Myocardial infarction within 1 year before randomization
- Uncontrolled cardiac arrhythmia
- Active bleeding or clinically significant major bleeding episode within the last 4 weeks
- Other invasive malignancy within 2 years, with the exception of adequately treated nonmelanoma skin cancer, localized cervical cancer, or low-risk prostate cancer
- Diagnosis of immunodeficiency or treatment with systemic corticosteroids or any other form of systemic immunosuppressive therapy within 7 days prior to study treatment
- History of autoimmune disease treated with systemic corticosteroids and/or other disease-modifying agents in the last 2 years
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David A Liebner
Ohio State University Comprehensive Cancer Center
Central Study Contacts
The Ohio State University Comprehensive Cancer Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 11, 2026
First Posted
September 16, 2026
Study Start (Estimated)
December 1, 2026
Primary Completion (Estimated)
December 31, 2028
Study Completion (Estimated)
December 31, 2028
Last Updated
September 16, 2026
Record last verified: 2026-09