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Soft Tissue SarcomaPhase 1NCT05813327

Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma

A Phase 1 study testing ADI PEG20, Ifosfamide and Radiotherapy in people with Soft Tissue Sarcoma and Sts, run by Washington University School of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

In this study, patients with soft tissue sarcoma (STS) will receive ADI-PEG 20 and ifosfamide in combination with radiation as neoadjuvant therapy. In phase I of the study, up to 5 dose levels will be tested to find the recommended phase II dose (RP2D), after which patients enrolling to phase II will be treated at… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Soft Tissue Sarcoma, Sts, Sarcoma,Soft Tissue
What is being tested?
ADI PEG20, Ifosfamide and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
14 Mar 2024to 22 Jul 2026
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

  • Patients with pathologically proven diagnosis of grade 2-3 (intermediate or high grade) soft tissue sarcoma of the trunk or extremities with size ≥5 cm by clinical or radiographic assessment that is appropriate for ifosfamide therapy. Patients must be planning to undergo treatment with curative intent.
  • Patients with sufficient tumor tissue for correlative analyses. Patients without sufficient tissue may be allowed to enroll on a case-by-case basis with permission of sponsor-investigator.
  • Staging workup shows no definitive evidence of distant metastasis and there is planned definitive surgical resection of the primary tumor.
  • At least 18 years of age at time of consent.
  • ECOG performance status ≤ 1
  • Adequate bone marrow, coagulation, and organ function as defined below:
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  • Absolute neutrophil count ≥ 1.5 K/cumm
  • Platelets ≥ 100 K/cumm
  • Hemoglobin ≥ 9 g/dL (no transfusions within 7 days of C1D-7)
  • International Normalized Ratio (INR) ≤ 1.5 x IULN or prothrombin time (PT) ≤ 1.5 x IULN, and partial thromboplastin time (aPTT or PTT) ≤ 1.5 x IULN (inclusion only applicable to subjects not using anticoagulation).
  • Total bilirubin ≤ 1.5 x IULN (except for patients with Gilbert's Syndrome, who must have a total bilirubin <3 mg/dL)
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
  • Creatinine clearance ≥ 60 mL/min/1.73^2 by MDRD
  • The effects of the study therapy on the developing human fetus are unknown. For this reason and because chemotherapeutics are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and 12 months after completion of the study. Should a woman or female partner become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Highly effective methods of birth control are defined as those that results in a low failure rate (that is, <1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), partner or a vasectomized partner. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. Exceptions: Exceptions: Females not of child-bearing potential due to surgical sterilization (at least 6 weeks following tubal ligation, hysterectomy, or surgical bilateral oophorectomy with or without hysterectomy) confirmed by medical history; or postmenopausal female. A postmenopausal female is a female meeting either of the following criteria: Spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example, oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators [SERMs], or chemotherapy). Spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone (FSH) level >40 IUnits/L
  • Ability to understand and willingness to sign an IRB approved written informed consent document.

Who cannot join

  • Pure well-differentiated liposarcoma, low grade STS, Kaposi sarcoma, bone sarcomas, cartilage sarcomas, or GIST.
  • Definitive clinical or radiologic evidence of metastatic disease; indeterminate lung nodules less than 5 mm are acceptable.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Currently receiving any other investigational agents.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, ifosfamide, PEGylated compounds, or other agents used in the study.
  • Prior systemic chemotherapy for the study cancer (sarcoma); note that prior chemotherapy for a different cancer (including a different sarcoma) is allowable if given greater than three years prior. However, unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (Grade 2 or 3 toxicities from prior antitumor therapy that are considered irreversible [defined as having been present and stable for > 6 months] may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by the sponsor-investigator.
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  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
  • Clinically significant bleeding within 4 weeks of C1D-7, current use of direct thrombin inhibitors unless these medications can be safely discontinued 14 days prior to C1D-7. Note: Low molecular weight heparin and factor Xa inhibitors are permitted.
  • Concomitant use of the below medications is restricted during the study:
  • All herbal medicines (e.g., St. John's wort), and supplements, within the 6 days prior to C1D-7. Standard adult multi-vitamin is allowed.
  • CYP2C8 substrates with a narrow therapeutic window within the 6 days prior to C1D-7.
  • No live vaccines within 6 days of C1D-7.
  • Patients with active infection requiring IV antibiotics within 2 weeks of C1D-7
  • The patient has a serious cardiac condition, such as congestive heart failure; New York Heart Association Class III/IV heart disease; unstable angina pectoris, cardiac stenting within 6 months of C1D-7; myocardial infarction within 6 months of C1D-7; valvulopathy that is severe, moderate, and deemed clinically significant; or arrhythmias that are symptomatic or require treatment.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of C1D-7.
  • Patients with known active Hepatitis B or C or HIV.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I/II Trial of Neoadjuvant ADI-PEG 20 in Combination With Ifosfamide and Radiotherapy in Soft Tissue Sarcoma (STS)

In this study, patients with soft tissue sarcoma (STS) will receive ADI-PEG 20 and ifosfamide in combination with radiation as neoadjuvant therapy. In phase I of the study, up to 5 dose levels will be tested to find the recommended phase II dose (RP2D), after which patients enrolling to phase II will be treated at that dose level to assess efficacy.

Being tested
ADI PEG20, Ifosfamide, Radiotherapy, Mesna
Keywords
arginine starvation, ADI-PEG20, ifosfamide, radiotherapy, radiation therapy, ASS1 expression
Medical subject headings
Sarcoma, Ichthyosis, X-Linked

What participants receive

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

  • ADI PEG20Drug

    Also called PEGylated arginine deiminase

    ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m^2 via intramuscular injection into either the deltoid or gluteal muscle.

  • IfosfamideDrug

    Also called ifex

    Ifosfamide will be administered intravenously per package insert and institutional practice on Days 1 through 5 of all 3 cycles.

  • RadiotherapyRadiation

    Radiotherapy will begin on C2D1 and will continue as per institutional practice.

  • MesnaDrug

    Also called sodium 2-mercaptoethane sulfonate

    Mesna will be administered for supportive care either intravenously or by mouth per package insert and institutional practice on Days 1 through 5 of all 3 cycles.

Study groups in NCT05813327
Study groupRoleWhat they receive
Phase I: ADI-PEG 20 + ifosfamide + radiotherapyExperimentalPatients will receive ADI-PEG 20 on Day -7 of Cycle 1 and Days 1, 8, and 15 of each of three 21-day cycles, and ifosfamide per dose escalation/de-escalation schedule on days 1 through 5 of each cycle. Mesna will be given on days 1 through 5 with ifosfamide as supportive care. Patients will also receive radiotherapy (XRT) starting on Week 4.
Receives: Drug: ADI PEG20; Drug: Ifosfamide; Radiation: Radiotherapy; Drug: Mesna
Phase II: ADI-PEG 20 + ifosfamide + radiotherapyExperimentalPatients will receive ADI-PEG 20 on Day -7 of Cycle 1 and Days 1, 8, and 15 of each of three 21-day cycles, and ifosfamide per the RP2D determined in Phase I of the study on days 1 through 5 of each cycle. Mesna will be given on days 1 through 5 with ifosfamide as supportive care. Patients will also receive radiotherapy (XRT) starting on Week 4.
Receives: Drug: ADI PEG20; Drug: Ifosfamide; Radiation: Radiotherapy; Drug: Mesna

What is being measured

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

  1. Treatment-related serious adverse event (SAE) rate

    An adverse event is considered serious if, in the view of the investigator, it results in any of the following:

    • Death
    • A life threatening adverse event
    • Inpatient hospitalization or prolongation of existing hospitalization
    • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
    • A congenital anomaly/birth defect
    • Any other important medical event that does not fit the criteria above but, based upon appropriate medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above

    Measured: From start of study treatment through 30 days from end of neoadjuvant treatment (estimated to be 14 weeks)

  2. Recommended Phase II dose (Phase I only)

    The MTD is defined as the highest dose level at which no more than 1 out of 6 patients experienced DLT at the end of Cycle 2. Dose escalations will proceed until the MTD has been reached or until Dose Level 3, and this dose level will then be defined as the Recommended Phase 2 Dose (RP2D).

    Measured: From start of study treatment through 2 cycles of treatment (estimated to be 7 weeks)

Secondary outcomes (6)

  1. Percent necrosis in final surgical specimen

    Defined as the proportion of patients with a necrosis in the final surgical specimen.

    Measured: At time of surgical resection (estimated to be 16 weeks)

  2. Pathologic complete response (pCR) in final surgical specimen

    Defined as the proportion of patients with a pCR confirmed in the final surgical specimen.

    Measured: At time of surgical resection (estimated to be 16 weeks)

  3. Percent local failure (%LF)

    Defined as the proportion of patients with a local failure, which is either local tumor recurrence or local tumor progression.

    Measured: At 2 years from surgical resection (estimated to be 120 weeks)

  4. Disease free survival (DFS)

    Defined as the time from start of treatment to time of recurrence or death, whichever occurs first.

    Measured: At 2 years from surgical resection (estimated to be 120 weeks)

  5. Overall survival (OS)

    Defined as the time from start of treatment to death from any cause.

    Measured: At 2 years from surgical resection (estimated to be 120 weeks)

  6. Response rate per RECIST 1.1

    Measured: After completion of treatment but prior to surgery (estimated to be 10 weeks)

Timeline

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

  1. First posted14 Apr 2023
  2. Study start14 Mar 2024
  3. Primary completion10 Apr 2026
  4. Study completion22 Jul 2026

Why it stopped: Polaris decided to close to accrual.

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05813327
Sponsor's protocol ID
202305073
Status last verified
Aug 2026
First submitted
2 Apr 2023
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ADI PEG20, Ifosfamide and Radiotherapy in people with Soft Tissue Sarcoma and Sts, run by Washington University School of Medicine 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 15 inclusion and 16 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: stopped early, as of the sponsor's last update on 3 Sep 2026. 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 was stopped early (reason given: Polaris decided to close to accrual.). Results are not available in the source record.

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?

Treatment-related serious adverse event (SAE) rate (time frame: From start of study treatment through 30 days from end of neoadjuvant treatment (estimated to be 14 weeks)). The study lists 2 primary outcomes in all. 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 NCT05813327.

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 3 Sep 2026.

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