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This is a prospective, Phase II, open-label, two-arm parallel study evaluating the efficacy and safety of combined treatment (L-Ornithine L-Aspartate, N-Acetylcysteine) with CDK4/6 inhibitors and Fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer (ABC) who have progressed on prior standard therapy including CDK4/6 inhibitors and endocrine therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CDK4/6 inhibitor + Fulvestrant + L-Ornithine L-Aspartate | Experimental |
| |
| CDK4/6 inhibitor + Fulvestrant + N-Acetylcysteine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Ornithine L-Aspartate | Drug | 3g orally three times daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | Baseline until disease progression or loss of clinical benefit, assessed up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate (DCR) | Baseline through end of study, assessed up to 6 months | |
| Progression Free Survival (PFS) | Randomization to death from any cause, through the end of study, assessed up to 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhiming Shao, Professor | Contact | 08664175590 | 88807 | zhimin_shao@yeah.net |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | 200032 | China |
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| CDK4/6 inhibitor | Drug | at the physician's choice |
|
| Fulvestrant | Drug | 500mg IM on Days 1 & 15 of Cycle 1, then Day 1 of subsequent cycles |
|
| N-Acetylcysteine (NAC) Treatment | Drug | 600mg orally twice daily |
|
| Safety and treatment-related AEs (assessed by CTCAE v5.0) | The total count and percentage of participants experiencing treatment-related AEs, classified by severity (Grades 1-5) according to CTCAE v5.0 | Randomization to death from any cause, through the end of study, assessed up to 12 months |
| Biomarker analysis | Pre- and post-treatment samples (tumor tissue, blood, and feces) will be analyzed for blood ammonia levels, ammonia-related genes, cell functions, and microbes to predict therapy response | Baseline until disease progression or loss of clinical benefit, assessed up to 6 months |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C002939 | ornithylaspartate |
| D000077267 | Fulvestrant |
| D000111 | Acetylcysteine |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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