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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2023-02578 | Other Identifier | NCI- Clinical Trials Reporting Program |
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| Name | Class |
|---|---|
| United States Department of Defense | FED |
| Novartis Pharmaceuticals | INDUSTRY |
| Effector Therapeutics | INDUSTRY |
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The purpose of this study is to learn if adding a new drug that is targeted at a specific genetic change found in some breast tumors pre-operatively will slow the growth of the tumor more than standard anti-hormone therapy used to treat this type of breast cancer. Different therapies are being tested based on the specific gene changes in the tumor. Not every tumor will have a gene change that is being studied.
Primary Objective: To evaluate the efficacy of investigational agent compared with standard endocrine therapy in in reducing Ki67 values based on digital pathology (QuPath) from baseline to on-treatment biopsy after an specific treatment duration (i.e. 14 days) in ER-positive, HER2-negative tumors (tumor size ≥1 cm) with Ki67 ≥ 10%, for different integrative subtype categories identified at integrative subtype screening.
Secondary Objective: To evaluate the efficacy of investigational agent compared with standard endocrine therapy on the proportion of subjects with Ki67 < 10% after a specific treatment duration (i.e. 14 days)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IC1:Alpelisib in combination with Tamoxifen (closed to enrollment) | Experimental | Integrative subtype IC1, Treatment (14 days, - 2 or + 7 days): Take assigned alpelisib pills, 300 mg (two 150 mg tablets) with food, once daily by mouth. Tamoxifen pills, 20 mg once daily by mouth |
|
| IC1:Tamoxifen (closed to enrollment) | Active Comparator | Integrative subtype 1, Treatment (14 days, -2 to +7 days): Take assigned tamoxifen pills, 20 mg once daily by mouth |
|
| IC2:Zotatifin in combination with Fulvestrant | Experimental | Integrative subtype 2, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC2:Fulvestrant | Active Comparator | Integrative subtype 2, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC3:Zotatifin in combination with Fulvestrant | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alpelisib | Drug | Alpelisib 300 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Ki67 | The primary outcome is the percentage change in Ki67 expression comparing pre-treatment to on-treatment specimens. Ki67 values were log-transformed for analysis, and results are summarized as the mean percentage change with 95% confidence intervals. | Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Ki67 <10% On-treatment Measurement | The proportions of subjects with Ki67 less than 10% after treatment. The outcome will be reported as a number without dispersion. | 15 or 19 days, based on the duration specified for the assigned therapy |
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Inclusion Criteria:
Treatment Phase
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Caswell-Jin | Stanford Universiy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94304 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 2 or 6 Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg |
| FG001 | Cohort 2: Fulvestrant (Control Arm) | Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Fulvestrant: Fulvestrant 500 mg |
| FG002 | Cohort 3:Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg |
| FG003 | Cohort 3:Fulvestrant (Control Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1. Fulvestrant: Fulvestrant 500 mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Change in Ki67 | The primary outcome is the percentage change in Ki67 expression comparing pre-treatment to on-treatment specimens. Ki67 values were log-transformed for analysis, and results are summarized as the mean percentage change with 95% confidence intervals. | Posted | Mean | 95% Confidence Interval | percentage | Measured pre-treatment and after treatment 15 or 19 days, based on the duration specified for the assigned therapy |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 2: Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hematoma | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer Lee Caswell-Jin | Stanford University | (650) 498-6000 | caswell@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 20, 2023 | Dec 10, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C585539 | Alpelisib |
| D013629 | Tamoxifen |
| D000077267 | Fulvestrant |
| ID | Term |
|---|---|
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
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Integrative subtype 3, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC3:Fulvestrant | Active Comparator | Integrative subtype 3, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. on Day 1. |
|
| IC4:Zotatifin in combination with Fulvestrant | Experimental | Integrative subtype 4, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC4:Fulvestrant | Active Comparator | Integrative subtype 4, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1.. |
|
| IC6:Zotatifin in combination with Fulvestrant | Experimental | Integrative subtype 6, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC6:Fulvestrant | Active Comparator | Integrative subtype 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC7:Zotatifin in combination with Fulvestrant | Experimental | Integrative subtype 7, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC7:Fulvestrant | Active Comparator | Integrative subtype 7, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC8:Zotatifin in combination with Fulvestrant | Experimental | Integrative subtype 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) should be administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| IC8:Fulvestrant | Active Comparator | Integrative subtype 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant should be administered intramuscularly as two 5mL injection on Day 1. |
|
| Tamoxifen | Drug | Tamoxifen 20 mg |
|
|
| Zotatifin | Drug | Zotatifin 0.10mg/kg (by weight) |
|
|
| Fulvestrant | Drug | Fulvestrant 500 mg |
|
|
| BG001 | Cohort 2: Fulvestrant (Control Arm) | Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Fulvestrant: Fulvestrant 500 mg |
| BG002 | Cohort 3: Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg |
| BG003 | Cohort 3: Fulvestrant (Control Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1. Fulvestrant: Fulvestrant 500 mg |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Cohort 2: Fulvestrant (Control Arm) |
Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Fulvestrant: Fulvestrant 500 mg |
| OG002 | Cohort 3: Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg |
| OG003 | Cohort 3: Fulvestrant (Control Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1. Fulvestrant: Fulvestrant 500 mg |
|
|
| Secondary | Ki67 <10% On-treatment Measurement | The proportions of subjects with Ki67 less than 10% after treatment. The outcome will be reported as a number without dispersion. | Posted | Number | participants | 15 or 19 days, based on the duration specified for the assigned therapy |
|
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | Cohort 2: Fulvestrant (Control Arm) | Integrative subtype 2 or 6, Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Fulvestrant: Fulvestrant 500 mg | 0 | 2 | 0 | 2 | 2 | 2 |
| EG002 | Cohort 3:Zotatifin in Combination With Fulvestrant (Treatment Arm) | Integrative subtype 3, 4, 7, or 8, Treatment (14 days, - 2 to +7 days). Zotatifin (calculated by weight, 0.10 mg/kg) was administered as a 60-minute IV infusion on Days 1. A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. Zotatifin: Zotatifin 0.10mg/kg (by weight) Fulvestrant: Fulvestrant 500 mg | 0 | 7 | 0 | 7 | 7 | 7 |
| EG003 | Cohort 3: Fulvestrant (Control Arm) | Integrative subtype 3, 4, 7, or 8,Treatment (14 days, - 2 to +7 days) A total of 500 mg Fulvestrant was administered intramuscularly as two 5mL injection on Day 1. on Day 1. Fulvestrant: Fulvestrant 500 mg | 0 | 8 | 0 | 8 | 5 | 8 |
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Stomach pain | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Injection site reaction | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| CPK increased | Infections and infestations | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | Systematic Assessment |
|
| Dysesthesia | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Injection site reaction | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| hot flashes | Vascular disorders | Systematic Assessment |
|
| bruising | Investigations | Systematic Assessment |
|
| seroma | Injury, poisoning and procedural complications | Systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| 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 |