Trial Title:
Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma
NCT ID:
NCT05813327
Condition:
Soft Tissue Sarcoma
Sts
Sarcoma,Soft Tissue
Conditions: Official terms:
Sarcoma
Ifosfamide
Mesna
Conditions: Keywords:
arginine starvation
ADI-PEG20
ifosfamide
radiotherapy
radiation therapy
ASS1 expression
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ADI PEG20
Description:
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.
Arm group label:
Phase I: ADI-PEG 20 + ifosfamide + radiotherapy
Arm group label:
Phase II: ADI-PEG 20 + ifosfamide + radiotherapy
Other name:
PEGylated arginine deiminase
Intervention type:
Drug
Intervention name:
Ifosfamide
Description:
Ifosfamide will be administered intravenously per package insert and institutional
practice on Days 1 through 5 of all 3 cycles.
Arm group label:
Phase I: ADI-PEG 20 + ifosfamide + radiotherapy
Arm group label:
Phase II: ADI-PEG 20 + ifosfamide + radiotherapy
Other name:
ifex
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
Radiotherapy will begin on C2D1 and will continue as per institutional practice.
Arm group label:
Phase I: ADI-PEG 20 + ifosfamide + radiotherapy
Arm group label:
Phase II: ADI-PEG 20 + ifosfamide + radiotherapy
Intervention type:
Drug
Intervention name:
Mesna
Description:
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.
Arm group label:
Phase I: ADI-PEG 20 + ifosfamide + radiotherapy
Arm group label:
Phase II: ADI-PEG 20 + ifosfamide + radiotherapy
Other name:
sodium 2-mercaptoethane sulfonate
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 that dose level to assess
efficacy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 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.
- ECOG performance status ≤ 1
- Adequate bone marrow, coagulation, and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 10 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
- 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 by Cockcroft-Gault
- 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 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), sexual abstinence, or a vasectomized partner. 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 with 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).
- Ability to understand and willingness to sign an IRB approved written informed
consent document.
Exclusion Criteria:
- Well-differentiated liposarcoma or other low grade STS, Kaposi sarcoma, bone
sarcomas, cartilage sarcomas, and 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.
- 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 warfarin,
factor Xa inhibitors, and direct thrombin inhibitors unless these medications can be
safely discontinued 14 days prior to ADI-PEG 20 and ifosfamide administration. Note:
Low molecular weight heparin and prophylactic low dose warfarin are permitted.
PT/PTT must meet the inclusion criteria. Subjects taking warfarin must have their
INR followed closely.
- Concomitant use of the below medications is restricted during the study:
- All herbal medicines (e.g., St. John's wort), and supplements, within the 10
days prior to C1D-7. Standard adult multi-vitamin is allowed.
- CYP2C8 substrates with a narrow therapeutic window within the 14 days prior to
C1D-7.
- Medications known to cause QTc interval prolongation within 7 days prior to
C1D-7. Ondansetron is permitted for treatment of nausea and vomiting at the
discretion of the treating physician.
- No live vaccines within 2 weeks of C1D-7.
- Patients with active infection requiring IV antibiotics within 2 weeks of the first
dose of ADI-PEG 20.
- The patient has a serious cardiac condition, such as congestive heart failure; New
York Heart Association Class II/ III/IV heart disease; unstable angina pectoris,
cardiac stenting within 6 months of C1D-7; myocardial infarction within the 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mia Weiss, M.D.
Phone:
314-273-4703
Email:
m.c.weiss@wustl.edu
Investigator:
Last name:
Mia Weiss, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Brian Van Tine, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Angela Hirbe, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Douglas Adkins, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Stephanie Perkins, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Anthony J Apicelli, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Chongliang (Jason) Luo, Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Sasha Haarberg, Pharm.D., BCOP
Email:
Sub-Investigator
Investigator:
Last name:
Heather Benedict Hamilton, M.S.
Email:
Sub-Investigator
Start date:
March 14, 2024
Completion date:
January 15, 2028
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Polaris Group
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05813327
http://www.siteman.wustl.edu
