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.
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Fibrosarcoma
Malignant fibrous histiocytoma
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
Any prior surgery (apart from diagnostic biopsy), radiation therapy, or systemic therapy for management of present tumor. Patients with locally recurrent sarcoma after prior surgery alone are eligible for enrollment if other inclusion criteria are met
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Doxorubicin
DrugGiven IV
Ifosfamide
DrugGiven IV
Intensity-Modulated Radiation Therapy
RadiationUndergo IMRT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Pembrolizumab
Biological/VaccineGiven IV
Questionnaire Administration
Other interventionAncillary studies
Surgical Procedure
Procedure/SurgeryUndergo oncologic resection
Transthoracic Echocardiography Test
Procedure/SurgeryUndergo TTE
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.
Patient-reported quality of life (QOL)
Will be evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. A linear mixed-effects model will be used to assess changes in QOL over time, including random intercepts and slopes. The model will incorporate treatment group, time, baseline QOL score, and the treatment-by-time interaction as covariates.
Overall survival (OS)
Will be estimated using the Kaplan-Meier method and compared between treatment groups using the log-rank test. A Cox proportional hazards model will also be used to evaluate OS, adjusting for relevant covariates.
Loco-regional DFS
Will be defined as clinical or biopsy-confirmed recurrence at the primary tumor site, regional nodal involvement, and loco-regional relapse. Will be estimated using the Kaplan-Meier method and compared between treatment groups using the log-rank test. A Cox proportional hazards model will also be used to evaluate loco-regional DFS, adjusting for relevant covariates.
Distant DFS
Will be defined as clinical or biopsy-confirmed recurrence at a distant site distinct from the primary tumor site. Will be estimated using the Kaplan-Meier method and compared between treatment groups using the log-rank test. A Cox proportional hazards model will also be used to evaluate distant DFS, adjusting for relevant covariates.
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Ohio State University Comprehensive Cancer Center
Lead sponsor
Patient-Centered Outcomes Research Institute
Collaborator
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