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Stage III Adult Soft Tissue SarcomaPhase 1NCT02180698

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

A Phase 1 study testing Laboratory Biomarker Analysis, Radiation Therapy and TLR4 Agonist GLA-SE in people with Stage III Adult Soft Tissue Sarcoma and Stage IV Adult Soft Tissue Sarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Radiation Therapy and TLR4 Agonist GLA-SE
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
17 Nov 2014to 7 Oct 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase I Study to Determine the Safety of the Combination of Stable-Emulsion Formulation of Glucopyranosyl Lipid A (GLA-SE) With Radiation in Patients With Metastatic Sarcoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety of weekly injections of GLA-SE (TLR4 agonist GLA-SE) in combination with palliative radiation in patients with metastatic sarcoma.

SECONDARY OBJECTIVES:

  1. To look for preliminary evidence of efficacy at distant tumor sites following the combination of radiation and intra-tumor injection of GLA-SE.

II. To analyze changes in tumor-immune infiltrates following radiation and intra-tumor injection of GLA-SE.

OUTLINE: This is a dose-escalation study of TLR4 agonist GLA-SE.

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.

After completion of study treatment, patients are followed up every 6 weeks for 6 months and then every 3 months for up to 1 year.

Being tested
Laboratory Biomarker Analysis, Radiation Therapy, TLR4 Agonist GLA-SE
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation

    Undergo radiation therapy

  • TLR4 Agonist GLA-SEDrug

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

    Given intratumorally

Study groups in NCT02180698
Study groupRoleWhat they receive
Treatment (TLR4 agonist GLA-SE, radiation therapy)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Radiation: Radiation Therapy; Drug: TLR4 Agonist GLA-SE

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to week 9

Secondary outcomes (7)

  1. Change in biomarker outcomes from the peripheral blood

    Summary statistics will be used to describe changes across time. In addition, the time course of biomarker outcomes from the peripheral blood will be investigated graphically, by summary plots or individual patient plots. If there is suggestion of meaningful trend, methods such as linear mixed models may be used to characterize the pattern of change over time.

    Measured: Baseline up to 1 year

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

    Categorical data analysis and logistic regression will be used to evaluate the associations between correlative measures and clinical outcome (e.g., response, clinical benefit, time to progression, progression-free survival, and survival).

    Measured: Up to 1 year

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

    Tumor infiltrating lymphocytes will be analyzed directly by flow and grown in vitro so that functional characteristics can be analyzed. Metrics based on flow cytometry (e.g. cell phenotype and inhibitory receptor expression) will be reported both with respect to the mean florescence intensity of the staining as well as the absolute and relative numbers of positive and negative cells compared with established controls.

    Measured: Up to 1 year

  4. Progression free survival

    Categorical data analysis and logistic regression will be used to evaluate the associations between correlative measures and clinical outcome (e.g., response, clinical benefit, time to progression, progression-free survival, and survival). Kaplan-Meier methodology and Cox Proportional Hazards models will be used to evaluate time-to-event endpoints.

    Measured: Up to 1 year

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

    Categorical data analysis and logistic regression will be used to evaluate the associations between correlative measures and clinical outcome (e.g., response, clinical benefit, time to progression, progression-free survival, and survival).

    Measured: Up to 1 year

  6. Survival

    Categorical data analysis and logistic regression will be used to evaluate the associations between correlative measures and clinical outcome (e.g., response, clinical benefit, time to progression, progression-free survival, and survival). Kaplan-Meier methodology and Cox Proportional Hazards models will be used to evaluate time-to-event endpoints.

    Measured: Up to 1 year

  7. Time to progression

    Categorical data analysis and logistic regression will be used to evaluate the associations between correlative measures and clinical outcome (e.g., response, clinical benefit, time to progression, progression-free survival, and survival). Kaplan-Meier methodology and Cox Proportional Hazards models will be used to evaluate time-to-event endpoints.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2014 (estimated)
  2. Study start17 Nov 2014
  3. Primary completion7 Oct 2016
  4. Study completion7 Oct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02180698
Sponsor's protocol ID
9145
Other IDs
NCI-2014-01299, 9145, P30CA015704
Status last verified
Nov 2019
First submitted
1 Jul 2014
Last updated
6 Nov 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 37824131

  • 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.

    PubMed 35115306

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Radiation Therapy and TLR4 Agonist GLA-SE in people with Stage III Adult Soft Tissue Sarcoma and Stage IV Adult Soft Tissue Sarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to week 9). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02180698, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2019.

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