Fluorescent Aided Resection and Evaluation of Soft Tissue Sarcomas (FLARES)

This will be a prospective pilot study that will evaluate 20 patients who were diagnosed with FNCLCC Grade 2 or 3 soft tissue sarcomas and will undergo surgical resection. Based upon the FDA label, successful protocols used for intraoperative fluorescence-guided visualization for glioma resections, and on drug company current dosing recommendation for this study, patients will be administered 20 mg/kg body weight of 5-ALA orally at 3-4 hours prior to surgery. The use of 5-ALA fluorescence will be relevant for evaluating the resected tumor per gross margins and identifying further areas of fluorescing tissues beyond the gross tumor margins.

Study Overview

• Status: Withdrawn
• Conditions: Soft Tissue Sarcoma; Soft Tissue Sarcoma Adult
• Intervention / Treatment: Drug: Aminolevulinic Acid

Detailed Description

PRIMARY OBJECTIVE: I. Demonstrate the feasibility of 5-ALA-aided fluorescent visualization of STS versus surrounding tissues.

SECONDARY OBJECTIVE:

I. Demonstrate the efficacy of tumor and surgical margin resections by a gross and histological analysis of fluorescing and non-fluorescing samples immediately after removal.

II. Assess the safety profile of fluorescence-guided surgery (FGS) for STS utilizing 5-ALA.

OUTLINE: Patients will be administered 20 mg/kg body weight of 5-ALA orally at 3-4 hours prior to surgical resection. Intraoperative fluorescence-guided visualization will be used for evaluating the resected tumor per gross margins and identifying further areas of fluorescing tissues beyond the gross tumor margins.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95827
      • University of California Davis Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological confirmation of any subtype of primary Grades 2 or 3 soft tissue sarcomas (STS), per biopsy evaluation by a pathologist, according to Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC).
• Treatment decision includes planned surgical resection of STS.
• Age ≥18 years at time of consent.
• ECOG Performance Status 0 - 1 (see Appendix)

• Hematology and blood chemistry parameters defined by:

  • Leukocytes ≥ 3 × 109/L
  • Absolute neutrophil count ≥ 1.5 × 109/L
  • Platelets ≥ 100 × 109/L, transfusions may be used to raise platelets to ≥ 100 × 109/L (no washout required)
  • Hemoglobin ≥ 9 g/dL, transfusions may be used to raise Hgb to ≥ 9 g/dL (no washout required)
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
  • Aspartate transaminase (AST) / alanine transaminase (ALT) ≤ 2.5 × institutional ULN
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine above institutional ULN
• Participants of reproductive potential must agree to using adequate contraception (e.g., hormonal or barrier method of birth control; abstinence, an intrauterine device) for the duration of study participation (including dosing interruptions) and up to 42 days after end of study intervention; or be surgically sterilized (e.g., hysterectomy, tubal ligation, or vasectomy).
• Ability to swallow study agent.
• Ability to understand and willingness to sign an informed consent form.
• Ability and stated willingness to adhere to the study visit schedule and other protocol procedures/requirements for the duration of the study.

Exclusion Criteria:

• Acute/chronic forms of porphyria.
• Uncontrolled, known concurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness.
• Patient has had chemotherapy, tumor resection, or radiation treatment ≤ 21 days prior to surgery.
• Simultaneous participation in another clinical trial ≤ 21 days of enrollment or during the duration of the study period.
• Planned use of other potentially phototoxic substances (e.g., St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones and tetracyclines), and topical preparations containing aminolevulinic acid (5-ALA) for 24 hours during the perioperative period (defined as 24 hours prior to surgery to up to 24 hours post surgery).
• Pregnant or planning to become pregnant during study participation or breastfeeding.
• Any condition that in the opinion of the investigator would prohibit the understanding or rendering of informed consent or interfere with the participant's safety or compliance while on 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: Aminolevulinic acid (5-ALA); 20 mg/kg body weight of 5-ALA orally at 3-4 hours prior to surgical resection. 5-ALA fluorescence will be used to evaluate the resected tumor per gross margins and identifying further areas of fluorescing tissues beyond the gross tumor margins.	Drug: Aminolevulinic Acid; Given PO; Other Names: 5-ALA; Gleolan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of 5-ALA-aided fluorescent visualization of STS versus surrounding tissues	Ability of 5-ALA to provide intraoperative fluorescent visualization of STS versus surrounding tissues as assessed by the fluorescence of the surgical bed and hemisected soft tissue sarcoma (STS) after resection. This will be assessed during the surgical procedure and recorded via imaging and videography to analyze fluorescent visualization	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of tumor and surgical margin resections by a gross and histological analysis of fluorescing and non-fluorescing samples immediately after removal.	Verification of margins and disease tissue by sarcoma pathologist.	Up to 2 years
Disease free survival.	Time to development of recurrent disease or death from any cause.	Up to 2 years
Incidence of treatment related adverse events.	Number of intervention-related adverse events (AEs) per NCI CTCAE v5.0 as assessed through patient reported outcomes.	Up to 2 years

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven W Thorpe, MD, University of California, Davis

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 2, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: 2074423

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No