ATI-450 in Combination With Paclitaxel or Capecitabine in Patients With Hormone Receptor-positive and HER2 Negative Metastatic Breast Cancer With Bone Metastasis

• Status: Not yet recruiting
• Trial end date: 2028-04-30
• Target enrollment: 150
• Participant gender: All

Summary

This is a dose-escalating phase I using a rolling 6 design and randomized phase II study of ATI-450 in combination with chemotherapy testing the hypothesis that the combination of chemotherapy (paclitaxel or capecitabine) and ATI-450 will improve progression-free survival and reduce bone turnover, improve patient bone density, improve patient quality of life, and improve clinical efficacy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborators: Aclaris Therapeutics, Inc.; United States Department of Defense
• Treatments: Bone Density Conservation Agents; Capecitabine; Paclitaxel

Criteria

Inclusion Criteria:

• Phase I: Biopsy-proven hormone receptor-positive, HER2 negative metastatic breast cancer with bone metastasis.

• Phase II: Biopsy-proven hormone receptor-positive, HER2 negative metastatic breast cancer with progressive bone metastasis per the latest tumor imaging studies.

• Measurable or non-measurable but evaluable disease by RECIST v 1.1.

• No more than one prior chemotherapy for metastatic disease (phase II only). There are no limits on prior endocrine therapy-based regimens.

• Phase I: Washout from prior chemotherapy other than capecitabine (for the capecitabine cohort) or paclitaxel (for the paclitaxel cohort) for 3 weeks or passed 5 half-lives and recovered AEs to grade 1 (except for alopecia).

• Phase II: Washout from prior chemotherapy for 3 weeks or passed 5 half-lives and recovered AEs to grade 1 (except for alopecia).

• A washout period of 1 week is required from the completion of radiation therapy.

• Phase I: Planning to start or on stable doses of capecitabine (for the capecitabine cohort: no less than 1000 mg/m2 BID, 14 days on and 7 days off) or paclitaxel (for the paclitaxel cohort: no less than 80 mg/m2 weekly dosing).

• Phase II: Candidate for initiating capecitabine or paclitaxel treatment per physician decision.

• 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 ≥ 3,000/mcL

• Absolute neutrophil count ≥ 1,500/mcL

• Platelets ≥ 100,000/mcL

• Total bilirubin ≤ 1.5 x IULN

• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

• Creatinine clearance > 60 mL/min by Cockcroft-Gault

• Prior treatment with denosumab and zoledronic acid is allowed if at least 4 weeks have passed before the start of study treatment.

• The effects of ATI-450 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and 30 days 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 90 days after completion of the study

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.

• Currently receiving any other investigational agents.

• Untreated brain metastases. Patients with treated brain metastases are eligible if they show no evidence of progression and are off steroids.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ATI-450 or other agents used in the study.

• 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).

• 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 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.