ATI-2231 for Solid Tumor Cancers

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

Trial Summary

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.

What data supports the effectiveness of the drug ATI-2231 for solid tumor cancers?

The research does not provide direct evidence for ATI-2231 in solid tumor cancers, but it mentions that Capecitabine (Xeloda), a component of the treatment, has shown effectiveness in hormone-resistant metastatic prostate cancer by reducing prostate-specific antigen levels and providing clinical benefits like pain reduction. ^{1 2 3 4 5}

What makes the drug ATI-2231 combined with Capecitabine unique for treating solid tumor cancers?

ATI-2231 combined with Capecitabine is unique because Capecitabine is an oral drug that becomes active specifically at the tumor site, potentially reducing side effects compared to traditional chemotherapy that affects the whole body. This targeted activation is designed to improve effectiveness and minimize harm to healthy tissues. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing a new drug called ATI-2231 in patients with serious types of cancer to determine the most effective dose.

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

Interventions

• ATI-2231
• Bisphosphonate
• Capecitabine
• Denosumab

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Capecitabine in hormone-resistant metastatic prostatic carcinoma - a phase II trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Comparing Clinical Outcomes for Radium-223: Do Older Patients Do Worse? [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Radium-223 for the treatment of bone metastases in castration-resistant prostate cancer: when and why. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

The changing role of radium-223 in metastatic castrate-resistant prostate cancer: has the EMA missed the mark with revising the label? [2020]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. Greece pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

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