Habitat Escalated Adaptive Therapy (HEAT), With Neoadjuvant Radiation for Soft Tissue Sarcoma

Phase 2 Clinical Trial of Radiomic Habitat-Directed Radiation Dose Escalation for High-Grade Soft Tissue Sarcoma

The purpose of the study is to utilize radiomic images to precisely locate areas of tumor that can be treated with dose escalation radiation therapy.

Study Overview

• Status: Recruiting
• Conditions: High Grade Sarcoma
• Intervention / Treatment: Radiation: Intensity Modulated Radiation Therapy (IMRT); Diagnostic test: MRI

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Inaya Lemus; Phone Number: 813-745-4233; Email: Inaya.Lemus@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Arash O Naghavi, MD, MS
      • Sub-Investigator: Marilyn Bui, MD, PhD
      • Sub-Investigator: Ricardo Gonzalez, PhD
      • Sub-Investigator: Nainesh Parikh, MD, MBA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• For women of childbearing potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 52 weeks after the end of radiation.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner 52 weeks after radiation.
• Agreement to adhere to Lifestyle Considerations (as outlined in protocol) throughout study duration.
• Pathologically (histologically or cytologically) proven diagnosis of high-grade (grade 2 or 3) Soft Tissue Sarcoma (STS) of the deep trunk and/or extremity. Clinical evidence should be documented, and may consist of pathology or imaging, and should be sufficient to estimate the size of the primary (for T stage)
• Primary site deemed resectable prior to the start of trial
• American Joint Committee on Cancer (AJCC) 8th edition staging T1-4 N0 M0, no evidence of distant metastases
• Patients must have clinically or radiographically evident measurable disease at the primary site.
• Pre-Radiation Therapy (RT) MRI within 4 weeks of the start of RT.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 3.
• Deemed a surgical candidate
• Participant agrees to blood and plasma preservation for future analysis.

Exclusion Criteria:

• Contraindications to an MRI
• Positive urine pregnancy test
• Gross total excision of primary STS, including an unplanned excision
• Superficial sarcoma located primarily in the subcutaneous or cutaneous tissue
• Prior radiation to the region of the study cancer that would result in overlap of radiation therapy fields.
• Participants with a medical condition or social situation that, at the discretion of the principal investigator, would preclude them from completion of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; Participants will receive pretreatment diagnostic MRIs to generate MRI habitats (images of tumor regions/subregions in different sequences). These images will identify radioresistant cells within the tumor to allow for more precise and higher doses of radiation to the resistant cells. Participants will then be treated with neoadjuvant external beam radiation by using the intensity modulated radiation (IMRT) technique, with dose painting (simultaneous integrated boost/SIB) to 70 Gray Units (Gy), 60 Gy, and 50 Gy in 25 fractions for habitats 1, 2, and 3, respectively.

Radiation: Intensity Modulated Radiation Therapy (IMRT); Participants will be treated with intensity modulated radiation therapy (IMRT) with photons, which is FDA (U.S. Food and Drug Administration) approved radiation delivery system.; Diagnostic test: MRI; Participants will receive pretreatment diagnostic MRIs to generate MRI habitats. These images will identify radioresistant cells within tumor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Favorable Pathologic Response (FPR)	Percentage of participants with Favorable Pathologic Response (FPR): tumor necrosis >/= 95% at time of surgery. FPR is associated with improved R0 resection rates, local control, distant control, and overall survival. Therefore, FPR acts as an early surrogate for outcome.	Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of tumor with clear margin and positive margin	Review of final tumor margin of the surgical specimen, defined as tumor at ink margin, will be conducted by pathologist. A clear margin (R0) or a positive margin (R1/R2) will be designated, along with the location of the margin, which will be radiographically correlated to the habitat . Surgical margins are independent predictors for local control.	Weeks 10-13

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	Disease control rate defined as the sum of complete response, partial response, and stable disease rates.	Up to 6 months
Overall Survival	Overall Survival defined as the time from date of initial treatment to date of death.	Up to 8 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Viewray Inc.
• Investigators: Principal Investigator: Arash O Naghavi, MD, MS, Moffitt Cancer Center

Publications and helpful links

General Publications

• Naghavi AO, Bryant JM, Kim Y, Weygand J, Redler G, Sim AJ, Miller J, Coucoules K, Michael LT, Gloria WE, Yang G, Rosenberg SA, Ahmed K, Bui MM, Henderson-Jackson EB, Lee A, Lee CD, Gonzalez RJ, Feygelman V, Eschrich SA, Scott JG, Torres-Roca J, Latifi K, Parikh N, Costello J. Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma. BMC Cancer. 2024 Apr 9;24(1):437. doi: 10.1186/s12885-024-12151-7.

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 18, 2022
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: MCC-21136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No