ATX-101 in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma

NCT05116683 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAT7079
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effectiveness of a new investigational drug, ATX-101, for the treatment of dedifferentiated liposarcoma (LPS) and leiomyosarcoma (LMS). ATX-101 is an intravenous (IV) drug which blocks the interaction of a protein called PCNA with a number of "stress response" proteins. These interactions are thought to be important for cancer cell survival and growth. ATX-101 may disrupt these interactions and therefore help treat the cancer. In this study, all patients will receive the same treatment. Most of the exams, tests, and procedures are part of the usual approach to medical care for this condition. However, some additional tests or procedures may be performed, and other tests may be performed more frequently than usual.

Conditions

Leiomyosarcoma; Liposarcoma

Keywords

LMS; LPS; ATX-101

Outcome Measures

Primary Outcomes (1)

• Progression Free Rate (PFR)

  The study will evaluate the preliminary efficacy of ATX-101 in advanced L-sarcomas (LMS, LPS) by measuring the PFR (progression free rate) at 12 weeks (PFR12). Progression evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression).

  12 weeks

Secondary Outcomes (5)

• Number of Adverse Events

  Up to approximately 7 months

• Objective Response Rate (ORR)

  Up to approximately 7 months

• Duration of the Response

  Up to approximately 7 months

• Median Progression Free Survival (PFS)

  Up to approximately 5 months

• Median Overall Survival (OS)

  Up to approximately 7 months

Study Arms (1)

ATX-101

EXPERIMENTAL

Patients will be treated with ATX-101 60 mg/m2 IV weekly in continuous 21 day cycles. Patients will receive premedication prior to the ATX-101 infusion to reduce the risk of infusion-related reactions.

Drug: ATX-101

Interventions

ATX-101 DRUG

Patients will be given ATX-101 at 60 mg/m2 IV weekly in continuous 21 day cycles.

Also known as: ATX-101 drug substance

ATX-101

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed dedifferentiated liposarcoma (LPS) or leiomyosarcoma
• ATX-101 in Sarcoma Phase II
• (LMS). Pathology review occurs at the center enrolling the patient on this trial.
• Disease must be locally advanced and unresectable or metastatic. Disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligible.
• Patients must have measurable disease by RECIST criteria version 1.1. In addition, the first 10 patients enrolled on the study must have a site of disease amenable to image-guided biopsy at minimal risk or less, and must agree to undergo this biopsy.
• Patients must evidence of disease progression, either clinically or radiographically, within the 12 weeks prior to study enrollment, as determined by the investigator enrolling the patient on the study.
• Patients must have been treated with at least one prior systemic regimen for advanced sarcoma: LMS: Anthracycline-based chemotherapy, or gemcitabine/docetaxel. LPS: No specification as to the prior treatment received. Neoadjuvant or adjuvant systemic therapy does not qualify as prior treatment unless completed within 6 months of disease relapse.
• Patients must be age 18 years or older. Because the safety of ATX-101 in patients less than 18 years of age has not been characterized, children are excluded from the present study.
• Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Patients must demonstrate normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Creatinine ≤ 1.5 times upper limit of normal OR
• Calculated creatinine clearance \> 45 mL/min\*
• Total bilirubin ≤ 1.5 times upper limit of normal\*\*

You may not qualify if:

• Patients must not have received treatment with any chemotherapy, immunotherapy, radiotherapy or an investigational agent for malignancy within the 21 days of initiating treatment on this protocol.
• Patients may not have received treatment with a small molecule targeted agent (including off-label or investigational use) within 14 days of initiating treatment on this protocol, provided this represents at least 7 half-lives for that agent.
• Toxic effects from any prior therapy (except alopecia) must have resolved to grade 1 or less according to NCI CTCAE v4.0 or to the patient's baseline by the time of initiating treatment on this protocol.
• Patients may not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, cerebrovascular accident within the last six months, uncontrolled diabetes mellitus, uncontrolled psychiatric illness or any other disease condition that would limit compliance with study requirements in the opinion of the principal investigator.
• Patients may not be pregnant or nursing. Pregnant women are excluded from this study because the teratogenic effects of ATX-101 have not been adequately studied. A negative pregnancy test must be documented 7 days or less prior to initiating treatment on this protocol. Because there is an unknown but potential risk for adverse events to nursing infants secondary to treatment of the mother with ATX-101, breastfeeding must be discontinued prior to enrollment.
• Patients may not have known active hepatitis B or C infection. In patients with a history of hepatitis B or C infection, resolution of infection must be demonstrated by negative serology for hepatitis B surface antigen (HBsAg) and/or negative hepatitis C virus (HCV) RNA.
• Patients may not have uncontrolled HIV/AIDS infection. However, HIV positive patients on highly active retroviral therapy (HAART) with an undetectable viral load and CD4 T-cell count above 200 may participate.
• Anticipated requirement for surgery during the study period or major surgery within 3 weeks of initiating treatment.
• Active central nervous system (CNS) metastases or leptomeningeal involvement. Patients with known CNS metastases must have received definitive radiotherapy or surgery at least 4 weeks prior to initiating treatment with imaging demonstrating no progression of disease over this interval.

Sponsors & Collaborators

• Benjamin Izar: lead

Study Sites (1)

Columbia University Irving Medical Center / NewYork-Presbyterian

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Leiomyosarcoma; Liposarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue

Results Point of Contact

• Title: Benjamin Izar, MD
• Organization: Columbia University

bi2175@cumc.columbia.edu

212-304-5871

Study Officials

• Benjamin Izar, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Division of Hematology/Oncology, Department of Medicine

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: November 11, 2021
• Study Start: January 11, 2022
• Primary Completion: October 27, 2022
• Study Completion: October 27, 2022
• Last Updated: December 6, 2023
• Results First Posted: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)