ATI-2231 in Advanced Solid Tumor Malignancies

November 28, 2023 updated by: Washington University School of Medicine

A Phase Ia Trial of ATI-2231 in Advanced Solid Tumor Malignancies

The purpose of this first-in-human study is to test ATI-2231 in advanced solid tumor malignancies with the goal of establishing the recommended Phase II dose of ATI-2231.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Biopsy-proven advanced solid tumor malignancy including head and neck cancer, non-small cell lung cancer, gastrointestinal adenocarcinoma, pancreatic adenocarcinoma, prostate cancer, bladder cancer, and breast cancer.
  • Eligible patients must have an advanced solid malignancy above, for which standard curative or palliative therapies do not exist or are no longer effective.
  • Measurable or non-measurable but evaluable disease by RECIST v 1.1.
  • Patients must have archival tissue sample available from prior metastatic biopsy. If no tissue is available, patient may still be able to enroll with PI approval.
  • At least 18 years of age.
  • ECOG performance status ≤ 2
  • Life expectancy of at least 12 weeks.

  • Adequate bone marrow and organ function as defined below:

    • Leukocytes ≥ 3 K/cumm
    • Absolute neutrophil count (ANC) ≥ 1.5 K/cumm
    • Platelets ≥ 100 K/cumm
    • Total bilirubin ≤ 1.5 x IULN (unless patient has known Gilberts disease)
    • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
    • Creatinine clearance > 60 mL/min by Cockcroft-Gault
  • The effects of ATI-2231on the developing human fetus are unknown. For this reason, women of childbearing potential and men who are heterosexually active must agree to use adequate contraception as specified in the protocol. Contraception should continue for 1 month (for women) or 3 months (for men) after the end of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

  • Patients may not have received the following investigational or SOC therapies within the below specified time frames prior to C1D1:

    • Denosumab or bisphosphonates within 4 weeks
    • Radiation therapy within 1 week
    • Systemic chemotherapy, including antibody drug conjugates with chemotherapy payload, within 3 weeks.
    • Immunotherapy within 3 weeks
    • Oral chemotherapy or molecularly targeted therapy within 5 half-lives of the agent.
    • Endocrine therapies do not have a required washout and may be continued until C1D1.
  • Untreated brain metastases. Patients with treated brain metastases are eligible if they show no evidence of progression and are off steroids or on stable/decreasing steroid dose.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ATI-2231.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  • Patients with known HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
  • Screening resting QTcF above 460 ms (average of triplicate).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ATI-2231 monotherapy dose escalation
  • Patients will receive single agent ATI-2231 at assigned dose levels (n=3-6 per dose level). Starting dose of 20 mg by mouth twice per day.
  • Each cycle is 21 days
Drug: ATI-2231
Provided by Aclaris Therapeutics, Inc.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants experiencing adverse events
Time Frame: From baseline through 30 days after end of treatment (estimated to be 7 months)
-Graded per CTCAE v. 5.0
From baseline through 30 days after end of treatment (estimated to be 7 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Changes in ATI-2231 pharmacokinetics (PK) as measured by time to peak drug concentration (Tmax)
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by elimination rate constant
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by apparent volume of distribution
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by apparent clearance
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by peak concentration (Cmax)
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 day 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by half-life (T1/2)
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by area under the curve (AUC0-24h)
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, and 24 hours post dose cycle 1 (estimated to be 1 day)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, and 24 hours post dose cycle 1 (estimated to be 1 day)
Changes in ATI-2231 pharmacokinetics (PK) as measured by area under the curve (AUC0-infinity)
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by area under the curve (AUC0-t)
Time Frame: Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 (estimated to be 2 days)
Pre-dose cycle 1 day 1, 1 hour, 2 hours, 4 hours, 6 hours, 10 hours, 24 hours, 30 hours, and 48 hours post dose cycle 1 (estimated to be 2 days)
Changes in ATI-2231 pharmacokinetics (PK) as measured by peak concentration (Cmax)
Time Frame: Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Changes in ATI-2231 pharmacokinetics (PK) as measured by trough concentration
Time Frame: Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Changes in ATI-2231 pharmacokinetics (PK) as measured by area under the curve (AUC0-t)
Time Frame: Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Changes in ATI-2231 pharmacokinetics (PK) as measured by time to peak drug concentration (Tmax)
Time Frame: Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
Pre-dose cycle 2 day 1 (each cycle is 21 days), 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours post dose cycle 2 day 1 (estimated to be 10 hours)
ATI-2231 pharmacokinetics (PK) as measured by trough concentration
Time Frame: Cycle 3 day 1 (each cycle is 21 days)
Cycle 3 day 1 (each cycle is 21 days)
ATI-2231 pharmacokinetics (PK) as measured by trough concentration
Time Frame: Cycle 4 day 1 (each cycle is 21 days)
Cycle 4 day 1 (each cycle is 21 days)
ATI-2231 pharmacokinetics (PK) as measured by trough concentration
Time Frame: Cycle 5 day 1 (each cycle is 21 days)
Cycle 5 day 1 (each cycle is 21 days)
ATI-2231 pharmacokinetics (PK) as measured by trough concentration
Time Frame: Cycle 6 day 1 (each cycle is 21 days)
Cycle 6 day 1 (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Aclaris Therapeutics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cynthia X Ma, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 15, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 31, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 30, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 29, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 28, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202306048

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual patient data may be shared upon request with other non-commercial researchers and the request will be reviewed by the study team after the publication.

IPD Sharing Time Frame

After the publication

IPD Sharing Access Criteria

Please email cynthiaxma@wustl.edu for requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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