RECRUITING

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

Conditions

Soft Tissue Sarcoma Sts Sarcoma,Soft Tissue arginine starvation ADI-PEG20 ifosfamide radiotherapy radiation therapy ASS1 expression

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-03-14

Study Completion:2028-01-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05813327

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Mia Weiss, M.D.

CONTACT

314-273-4703

m.c.weiss@wustl.edu

Principal Investigator

Mia Weiss, M.D.

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Mia Weiss, M.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-03-14

Study Completion Date2028-01-15

Study Record Updates

Study Start Date2024-03-14

Study Completion Date2028-01-15

Terms related to this study

Keywords Provided by Researchers

arginine starvation
ADI-PEG20
ifosfamide
radiotherapy
radiation therapy
ASS1 expression

Additional Relevant MeSH Terms

Soft Tissue Sarcoma
Sts
Sarcoma,Soft Tissue