ATI-2231 for Solid Tumor Cancers

No longer recruiting at 2 trial locations

Overseen By Katherine Clifton, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Denosumab, Bisphosphonates, others

Disqualifiers: Untreated brain metastases, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ATI-2231, for individuals with advanced solid tumor cancers such as head and neck, lung, and breast cancer, where other treatments have failed. The primary goal is to determine the safest dose for future studies. Participants will receive ATI-2231 alone to assess how the body processes it. Suitable candidates have a solid tumor cancer unresponsive to other treatments and access to a past biopsy sample from their cancer. As a Phase 1 trial, this research aims to understand how ATI-2231 works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires stopping certain medications before starting, such as denosumab or bisphosphonates (4 weeks), radiation therapy (1 week), systemic chemotherapy (3 weeks), and immunotherapy (3 weeks). However, endocrine therapies can be continued until the first day of the trial.

Is there any evidence suggesting that ATI-2231 is likely to be safe for humans?

Research has shown that ATI-2231 is under careful observation for safety in patients with advanced solid tumors. This treatment is in the early testing stages, so researchers are primarily assessing patient tolerance. During this phase, they closely monitor any side effects or adverse reactions to ensure patient safety. As this is the first human trial, detailed safety information is not yet available. However, the emphasis on safety ensures that any serious issues are quickly identified and addressed. Joining a clinical trial involves some risk, so discussing potential side effects with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ATI-2231 is unique because it introduces a novel chemical compound specifically designed to target solid tumor cancers. Unlike traditional chemotherapy drugs that often attack rapidly dividing cells indiscriminately, ATI-2231 aims to provide a more targeted approach, potentially reducing side effects and improving patient outcomes. Researchers are excited about ATI-2231 because it offers a new mechanism of action that might work where other treatments have been less effective, giving hope for more personalized and effective cancer therapies.

What evidence suggests that ATI-2231 might be an effective treatment for solid tumor cancers?

Research shows that ATI-2231, administered as monotherapy in this trial, is a pill targeting a protein linked to tumor growth. This drug aims to slow or stop the growth of cancer cells in solid tumors. Early results suggest it might be effective for cancers such as pancreatic and metastatic breast cancer. Although human data remains limited, the drug's action on specific proteins shows promise in preventing cancer spread. While still in early stages, the science behind ATI-2231 appears hopeful for combating difficult cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Cynthia X Ma, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

For the capecitabine cohort, you must have completed a 3-week washout period from any prior chemotherapy other than capecitabine and completely recovered all adverse events (AEs) to Grade 1 (except alopecia).

You have abstained from previous chemotherapy for three weeks or a sufficient amount of time has elapsed since your last dose that any adverse effects have been reduced to Grade 1 (excluding hair loss).

Your absolute neutrophil count is at least 1,500/mcL.

Exclusion Criteria

You have had an allergic reaction to drugs similar to ATI-2231 or other drugs being used in the study.

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.

History of acute, untreated skeletal related events (SRE) or active untreated SRE or a change or an anticipated change in the SOC antiresorptive agents after entering the study (Phase II only).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ATI-2231 monotherapy at assigned dose levels, with each cycle lasting 21 days

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ATI-2231
• Bisphosphonate
• Capecitabine
• Denosumab

How Is the Trial Designed?

Group I: ATI-2231 monotherapy dose escalation Experimental Treatment 1 Intervention

* 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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Aclaris Therapeutics, Inc.

Industry Sponsor

Trials

35

Recruited

4,900+

Published Research Related to This Trial

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, M., et al.[2022]

In a study of 42 patients with metastatic or locally advanced pancreatic cancer, capecitabine demonstrated a clinical benefit response in 24% of patients, improving pain intensity and overall performance status.

Capecitabine was generally well tolerated, with a 9.5% objective response rate, suggesting it may be a viable treatment option for further evaluation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. Cartwright, TH., Cohn, A., Varkey, JA., et al.[2022]

Capecitabine (Xeloda) is an effective treatment for advanced/metastatic breast cancer, showing a response rate of 20% in a phase 2 trial with a median survival time of 452 days for patients who were resistant to previous therapies.

The most common side effects reported were hand-foot syndrome and various blood-related issues, indicating that while Capecitabine can be beneficial, it also carries a risk of significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine. Nishida, M.[2018]

In a study of 45 patients with locally advanced rectal cancer, preoperative chemoradiation using capecitabine resulted in significant tumor downstaging, with 63% of primary tumors and 90% of lymph nodes showing downstaging, and a pathologic complete response in 31% of patients.

The treatment was found to be safe and well-tolerated, with no severe hematologic toxicities and manageable Grade 3 side effects, suggesting that capecitabine can effectively enhance surgical options, including sphincter-preserving surgeries for tumors near the anal verge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Kim, JS., Kim, JS., Cho, MJ., et al.[2022]

Radium-223 ((223)Ra) is an FDA-approved treatment for men with castration-resistant prostate cancer (CRPC) who have symptomatic bone metastases and no known visceral metastatic disease, showing increased survival compared to standard care in clinical trials.

While (223)Ra is generally well tolerated with up to 6 injections, common side effects include nausea, diarrhea, and various blood-related issues, indicating the need for further research on its long-term safety and potential use alongside chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases. McGann, S., Horton, ER.[2019]

Citations

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ATI-2231 for Solid Tumor Cancers · Info for Participants

This trial is testing a new drug called ATI-2231 in patients with serious types of cancer to determine the most effective dose. Show more. Do I need to stop my ...

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Press Release - Investor Overview - Aclaris Therapeutics

ATI-2231 (Oral MK2 Inhibitor): ATI-2231 is a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing ...

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ATI-2231 (MK2 inhibitor) - Molecular Sherlock - Substack

ATI-2231 is an oral MAP kinase-activated protein kinase 2 (MK2) inhibitor being developed by Aclaris Therapeutics (ACRS -0.27%↓) for the ...

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cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06177

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ATI-2231 may be used to slow or stop the growth of tumor cells as well as potentially to improve symptoms in patients with advanced solid tumors. Eligibility ...

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ATI-2231 in Advanced Solid Tumor Malignancies

ATI-2231 is being researched in a first-in-human study to determine the recommended Phase II dose and effectiveness for treating ...

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Aclaris Therapeutics Announces Top-line Results from 12- ...

ATI-2231 (Oral MK2 Inhibitor): ATI-2231 is a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing ...