5-AminoLevulinic Acid Aided Resection Margins in Sarcoma

Official title

5-AminoLevulinic Acid Aided Resection Margins in Sarcoma (5-ALARMS)

Overview

The goal of this study is to learn if the intervention using a fluorescent agent 5-Aminolevulinic acid (5-ALA) to aid in the surgical approach to visualize the soft-tissue sarcoma (STS) during surgical resection. 5-ALA goes through the blood stream and into the tumor tissue allowing it to light up when the surgeon uses a special light in the operating room. The technique is called 5-ALA fluorescence-guided surgery (FGS). The main question aims to answer if 5-ALA provide intraoperative fluorescent visualization of soft-tissue sarcoma versus surrounding tissue and demonstrate the efficacy of tumor and surgical margin resections by a gross and histological analysis of fluorescing and non-fluorescing samples immediately after removal. Participants will be asked to orally administer 5-ALA three to four hours prior to surgery in preoperative area.

Interventions

• Drug 5-ALA
  5-ALA), also known by its brand name Gleolan, is an intermediate in the heme synthesis pathway that has been studied in tumor resections, especially in intracranial tumor resections. One advantage of intraoperative visualization with 5-ALA is the ability to directly visualize fluorescent tumor in the surgical field using a headset-mounted devices with fluorescence in the visual wavelength in real-time.

Primary outcome measures

• Demonstrate the feasibility of 5-ALA aided fluorescent visualization of soft tissue sarcomas versus surrounding tissues [Time frame: From enrollment to 2 weeks]
• Surgeon survey results of intraoperative tumor fluorescence [Time frame: perioperative/periprocedural]

Secondary outcome measures (7)

• Demonstrate the efficacy of 5-ALA fluorescence in tumor resections by a histological analysis of non-fluorescing samples after tumor removal [Time frame: Day of Surgery]
• Demonstrate the efficacy of 5-ALA fluorescence in tumor resections by a histological analysis of fluorescing samples after tumor removal [Time frame: Day of surgery]
• Demonstrate the efficacy of 5-ALA fluorescence in tumor resections by a histological analysis of fluorescing samples after tumor removal [Time frame: Day of surgery]
• Determine oncologic outcomes for patients enrolled [Time frame: From enrollment to 2 years]
• Patient Reported Outcomes [Time frame: From enrollment to 2 years]
• Patient Reported Outcomes [Time frame: From enrollment to 2 years.]
• Patient Reported Outcomes [Time frame: From enrollment to 2 years.]

Eligibility criteria

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.
• Hematology and blood chemistry parameters defined by:

• Leukocytes ≥ 3 × 10(9)/L
• Absolute neutrophil count ≥ 1.5 × 10(9)/L
• Platelets ≥ 100 × 109/L, transfusions may be used to raise platelets to ≥ 100 × 10(9)/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.

Inclusion of Minorities and Other Underrepresented Populations Recruitment is open and encouraged to all genders, all minorities, and underrepresented populations. Although distributions may vary by disease type, our recruitment procedures have been developed to enroll participants who are representative of the respective target population.

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 is 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• University of Colorado Hospital — Aurora

Publications

• Teixidor P, Arraez MA, Villalba G, Garcia R, Tardaguila M, Gonzalez JJ, Rimbau J, Vidal X, Montane E. Safety and Efficacy of 5-Aminolevulinic Acid for High Grade Glioma in Usual Clinical Practice: A Prospective Cohort Study. PLoS One. 2016 Feb 17;11(2):e0149244. doi: 10.1371/journal.pone.0149244. eCollection 2016. PMID 26885645
• Giantini-Larsen AM, Kharas N, Pisapia D, Schwartz TH. Histology of high-grade glioma samples resected using 5-ALA fluorescent headlight and loupe combination. Acta Neurochir (Wien). 2023 Feb;165(2):567-575. doi: 10.1007/s00701-023-05496-8. Epub 2023 Jan 19. PMID 36656388
• Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9. PMID 16648043
• Schupper AJ, Baron RB, Cheung W, Rodriguez J, Kalkanis SN, Chohan MO, Andersen BJ, Chamoun R, Nahed BV, Zacharia BE, Kennedy J, Moulding HD, Zucker L, Chicoine MR, Olson JJ, Jensen RL, Sherman JH, Zhang X, Price G, Fowkes M, Germano IM, Carter BS, Hadjipanayis CG, Yong RL. 5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study. J Neurosurg PMID 34624862
• Mahmoudi K, Garvey KL, Bouras A, Cramer G, Stepp H, Jesu Raj JG, Bozec D, Busch TM, Hadjipanayis CG. 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. J Neurooncol. 2019 Feb;141(3):595-607. doi: 10.1007/s11060-019-03103-4. Epub 2019 Jan 18. PMID 30659522
• Guder WK, Hartmann W, Buhles C, Burdack M, Busch M, Dunker N, Hardes J, Dirksen U, Bauer S, Streitburger A. 5-ALA-mediated fluorescence of musculoskeletal tumors in a chick chorio-allantoic membrane model: preclinical in vivo qualification analysis as a fluorescence-guided surgery agent in Orthopedic Oncology. J Orthop Surg Res. 2022 Jan 15;17(1):34. doi: 10.1186/s13018-022-02931-x. PMID 35033148
• Kenan S, Liang H, Goodman HJ, Jacobs AJ, Chan A, Grande DA, Levin AS. 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study. J Orthop Surg Res. 2020 Mar 5;15(1):94. doi: 10.1186/s13018-020-01606-9. PMID 32138774
• Endo M, Lin PP. Surgical margins in the management of extremity soft tissue sarcoma. Chin Clin Oncol. 2018 Aug;7(4):37. doi: 10.21037/cco.2018.08.10. PMID 30173528

Identifiers

NCT: NCT07038278 · 24-2149.cc

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗