TLR4 Agonist GLA-SE and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma That Is Metastatic or Cannot Be Removed by Surgery

NCT02180698 | Completed Phase 1 DMC

• 3 other identifiers: 9145NCI-2014-01299P30CA015704
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I clinical trial studies the side effects and best dose of toll-like receptor 4 (TLR4) agonist glucopyranosyl lipid A (GLA)-stable-emulsion (SE) when given together with radiation therapy in treating patients with soft tissue sarcoma that has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). TLR4 agonist GLA-SE may stimulate the immune system to kill sarcoma cells. Radiation therapy uses high energy x rays to kill tumor cells. Giving TLR4 agonist GLA-SE with radiation therapy may be a better treatment to treat sarcoma that cannot be removed by surgery.

Conditions

Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Incidence of severe adverse events, defined as any grade 3 or higher adverse event (AE) according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

  The highest toxicity grades per patient will be tabulated for AEs and laboratory measurements as will the numbers and percentages of patients reporting AEs.

  Up to week 9

Secondary Outcomes (7)

• Change in biomarker outcomes from the peripheral blood

  Baseline up to 1 year

• Clinical benefit based on RECIST v1.1 and iRRC evaluations

  Up to 1 year

• Immune infiltrates, measured quantitatively as number of cells per unit area

  Up to 1 year

• Progression free survival

  Up to 1 year

• Response based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 and immune-related-response criteria (iRRC) evaluations

  Up to 1 year

Study Arms (1)

Treatment (TLR4 agonist GLA-SE, radiation therapy)

EXPERIMENTAL

Patients receive TLR4 agonist GLA-SE intratumorally once weekly for 8 weeks. Within 2 weeks of starting treatment, patients also undergo radiation therapy over 2 weeks for a total of 5-6 fractions.

Other: Laboratory Biomarker Analysis; Radiation: Radiation Therapy; Drug: TLR4 Agonist GLA-SE

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (TLR4 agonist GLA-SE, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (TLR4 agonist GLA-SE, radiation therapy)

TLR4 Agonist GLA-SE DRUG

Given intratumorally

Also known as: GLA-SE, Glucopyranosyl Lipid A in Stable Emulsion, Glucopyranosyl Lipid Adjuvant-Stable Emulsion, Toll-like Receptor 4 Agonist GLA-SE

Treatment (TLR4 agonist GLA-SE, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of metastatic or unresectable sarcoma
• Patient must have a palpable, superficial tumor, safely accessible for bedside injection that will be radiated and can be accurately localized and stabilized if needed
• Patient must have consulted with a radiation oncologist who is planning radiation; radiation should be completed within a 2-week window from start to finish
• Patient must be willing to undergo biopsies as specified by the protocol; the biopsy requirement can only be waived if deemed unsafe by the patient's treating physician or the principal investigator (PI)
• Zubrod (Eastern Cooperative Oncology Group \[ECOG\]) performance status of '0-2'
• Serum creatinine =\< 1.5 times the upper limit of normal
• Total bilirubin =\< 1.5 times the upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times the upper limit of normal
• Prothrombin time (PT) =\< 1.5 times the upper limit of normal
• Partial thromboplastin time (PTT) =\< 1.5 times the upper limit of normal
• Absolute neutrophil \> 1000/uL
• Platelet count \> 75,000/uL
• For patients who will be entering the "expansion phase" of the trial, the patient must be able to safely delay radiation by at least 6 weeks

You may not qualify if:

• Pregnant women, nursing women, men and women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to study entry
• Known active symptomatic congestive heart failure
• Known clinically significant hypotension
• Known newly diagnosed cardiac arrhythmia; patients with an arrhythmia that has been stable for at least 3 months will be allowed to participate
• Known untreated central nervous system (CNS) metastasis
• Patients with known systemic infections requiring antibiotics or chronic maintenance/suppressive therapy
• Systemic anticancer therapy (chemotherapy, "biologics", immunotherapy) less than two weeks prior to starting radiation
• Known clinically significant autoimmune disorders requiring on-going systemic immune-suppression for control
• Current treatment with steroids
• Patients who are known to be human immunodeficiency virus (HIV) positive must have a normal cluster of differentiation (CD)4 count and undetectable viral load
• Current treatment with warfarin; for patients not on an anti-platelet agent such as aspirin, other anticoagulation is acceptable so long as the treating physician feels that it is safe to hold it on the day of the biopsy until after the biopsy has been safely completed
• Known allergy(ies) to any component of the study agent GLA-SE including egg lecithin

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Seo YD, Lu H, Black G, Smythe K, Yu Y, Hsu C, Ng J, Hermida de Viveiros P, Warren EH, Schroeder BA, O'Malley RB, Cranmer LD, Loggers ET, Wagner MJ, Bonham L, Pillarisetty VG, Kane G, Berglund P, Hsu FJ, Mi X, Alexiev BA, Pierce RH, Riddell SR, Jones RL, Ter Meulen J, Kim EY, Pollack SM. Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy in Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial. JAMA Oncol. 2023 Dec 1;9(12):1660-1668. doi: 10.1001/jamaoncol.2023.4015.

  PMID: 37824131 DERIVED

• Goff PH, Riolobos L, LaFleur BJ, Spraker MB, Seo YD, Smythe KS, Campbell JS, Pierce RH, Zhang Y, He Q, Kim EY, Schaub SK, Kane GM, Mantilla JG, Chen EY, Ricciotti R, Thompson MJ, Cranmer LD, Wagner MJ, Loggers ET, Jones RL, Murphy E, Blumenschein WM, McClanahan TK, Earls J, Flanagan KC, LaFranzo NA, Kim TS, Pollack SM. Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells. Clin Cancer Res. 2022 Apr 14;28(8):1701-1711. doi: 10.1158/1078-0432.CCR-21-4239.

  PMID: 35115306 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Radiotherapy; Radiation; glucopyranosyl lipid-A

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Seth Pollack

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2014
• First Posted: July 3, 2014
• Study Start: November 17, 2014
• Primary Completion: October 7, 2016
• Study Completion: October 7, 2016
• Last Updated: November 6, 2019

Record last verified: 2019-11

Locations

US (1)