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To assess longitudinal changes in allele frequency of ESR1 mutation in plasma in patients treated with Fulvestrant plus palbociclib compared to tamoxifen plus palbociclib
The primary objectives are to assess longitudinal changes in allele frequency of ESR1 mutation in plasma in patients treated with Fulvestrant plus palbociclib compared to tamoxifen plus palbociclib.
Patients with ER+ breast cancer who had 1 to 3 prior lines of endocrine therapy and up to one line of chemotherapy for MBC, excluding fulvestrant and tamoxifen, will be randomized in a 1:1 ratio to receive fulvestrant 500mg IM Q28 days with one extra dose on Day15 of the first cycle (as a loading dose) plus palbociclib 125mg/day PO on a 21 days on/7 days off schedule or tamoxifen 20mg PO daily plus palbociclib 125mg/day PO on a 21 days on/7 days off schedule.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Active Comparator | fulvestrant administered 500mg IM Q28 days plus palbociclib125mg/day PO on a 21 days on/7 days off schedule |
|
| Arm B | Active Comparator | Tamoxifen is administered orally, at a dose of20mg PO Qdaily plus palbociclib125mg/day PO on a 21 days on/7 days off schedule |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fulvestrant | Drug | 500mg IM Q28 days |
| |
| Tamoxifen |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | The duration of time from time of randomization to time of progression or death, whichever occurs first. Disease progression (PD) as defined by RECIST v1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The progression of non-target lesions or the appearance of one or more new lesions is also considered progression. PFS for a subject without an event will be censored on the date of last tumor assessment. If an interval of 6 months passes without a tumor assessment, PFS will be censored at the time of the earlier tumor assessment, even if an event (progressive disease or death) is later observed. | Up to 3 years and 351 days |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response (BOR) | The number of patients experiencing Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) per RECIST v1.1; Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): (CR) is disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions. (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions compared to baseline sum of target lesions, or any new lesions. It also includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
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For inclusion in the study subjects should fulfill the following criteria:
Signed informed consent
Patients must have histologically or cytologically confirmed invasive breast cancer that is ER+ (>1% staining) with radiographical or clinical evidence of metastatic disease
a. Measurable and/or non-measurable disease
Prior therapies:
Brain metastasis is allowed if previously treated, stable and off steroids for a minimum of 56 days
Age > 18 years
Male or female breast cancer is allowed
Patients may be pre- or post-menopausal; pre-menopausal patients must be on ovarian suppression and must be adequately suppressed on LHRH agonists with estradiol levels in the post-menopausal range
a. Premenopausal patients cannot be pregnant and must agree to adequate birth control in addition to ovarian suppression. Agreement by the patient and/or partner to use highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception. Contraception use should continue during the duration of study treatment and for at least 6 months after the last dose of study treatment.
ECOG performance status 0-2
Adequate bone marrow function as indicated by the following, within 14 days of enrollment:
Adequate liver function, as indicated by the following, within 14 days of enrollment.
Adequate hemostatic function as determined by PT, INR and aPTT < 1.5× ULN (unless on therapeutic coagulation, in which case the adequate level of anticoagulation will be determined by the investigator).
Adequate renal function, as indicated by creatinine ≤ 1.5 ULN.
Subjects should not enter the study if any of the following exclusion criteria are fulfilled
Prior therapy exclusions:
Washout of 2 weeks is required for aromatase inhibitors; washout of 4 weeks is required for, everolimus or other biological agents with the exception of Palbociclib.
Patients must not be receiving any other investigational agent.
Patients with symptomatic, untreated CNS metastases are not eligible.
Patients may not have significant concurrent illness, infection, pregnancy or lactation
Patients must not have a different active malignancy, except for skin basal cell carcinoma, skin squamous cell carcinoma and cervical intraepithelial neoplasia.
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| Name | Affiliation | Role |
|---|---|---|
| Shannon Puhalla, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Magee-Womens Hospital UPMC | Pittsburgh | Pennsylvania | 15213 | United States |
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All patients
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| ID | Title | Description |
|---|---|---|
| FG000 | Fulvestrant + Palbociclib | Fulvestrant: 500mg IM Q28 days Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
| FG001 | Tamoxifen + Palbociclib | Tamoxifen: 20mg PO Q-daily Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Fulvestrant + Palbociclib | Fulvestrant: 500mg IM Q28 days Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
| BG001 | Tamoxifen + Palbociclib | Tamoxifen: 20mg PO Q-daily Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Progression-free Survival (PFS) | The duration of time from time of randomization to time of progression or death, whichever occurs first. Disease progression (PD) as defined by RECIST v1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The progression of non-target lesions or the appearance of one or more new lesions is also considered progression. PFS for a subject without an event will be censored on the date of last tumor assessment. If an interval of 6 months passes without a tumor assessment, PFS will be censored at the time of the earlier tumor assessment, even if an event (progressive disease or death) is later observed. | Treated patients that were radiologically evaluable. | Posted | Median | 95% Confidence Interval | months | Up to 3 years and 351 days |
|
Up to 5 years
Common Terminology Criteria for Adverse Events (CTCAE) v4.0
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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 | Fulvestrant + Palbociclib | Fulvestrant: 500mg IM Q28 days Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Barbara Stadterman, MPH, MSCR | UPMC Hillman Cancer Center | 412-647-5554 | stadtermanbm@upmc.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 | Jul 16, 2020 | Mar 26, 2023 | 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 |
|---|---|
| D000077267 | Fulvestrant |
| D013629 | Tamoxifen |
| C500026 | palbociclib |
| ID | Term |
|---|---|
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 |
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| Drug |
20mg PO Qdaily |
|
| Palbociclib | Drug | Tamoxifen or Fulvestrant plus palbociclib125mg/day PO on a 21 days on/7 days off schedule |
|
| Up to 5 years |
| 6-Month Clinical Benefit Rate (CBR) | The number of patients experiencing Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1; Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): (CR) is disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions. | Up to 6 months |
| Clinical Benefit Rate (CBR) | The number of patients experiencing Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1; Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): (CR) is disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions. | Up to 5 years |
| Overall Survival (OS) | The median length of time from the start of treatment that patients remain alive. | Up to 5 years |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ECOG Performance Status (at study entry) | Eastern Cooperative Oncology Group (ECOG) Performance measures a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability. Scoring ranges from 0 to 5 and are as follows: 0 = Normal Activity, asymptomatic, 1 = Symptomatic, fully ambulatory, 2 = Symptomatic; in bed < 50% of time, 3 = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 = Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair, and, 5 = Death | Count of Participants | Participants |
|
| Fulvestrant + Palbociclib |
Fulvestrant: 500mg IM Q28 days Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
| OG001 | Tamoxifen + Palbociclib | Tamoxifen: 20mg PO Q-daily Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule |
|
|
| Secondary | Best Overall Response (BOR) | The number of patients experiencing Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) per RECIST v1.1; Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): (CR) is disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions. (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions compared to baseline sum of target lesions, or any new lesions. It also includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | Treated patients that were radiologically evaluable. | Posted | Count of Participants | Participants | Up to 5 years |
|
|
|
| Secondary | 6-Month Clinical Benefit Rate (CBR) | The number of patients experiencing Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1; Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): (CR) is disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions. | Treated patients that were radiologically evaluable. | Posted | Count of Participants | Participants | Up to 6 months |
|
|
|
| Secondary | Clinical Benefit Rate (CBR) | The number of patients experiencing Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1; Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): (CR) is disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions. | Treated patients that were radiologically evaluable. | Posted | Count of Participants | Participants | Up to 5 years |
|
|
|
| Secondary | Overall Survival (OS) | The median length of time from the start of treatment that patients remain alive. | All enrolled patients. | Posted | Median | 95% Confidence Interval | months | Up to 5 years |
|
|
|
| 1 |
| 5 |
| 2 |
| 5 |
| 5 |
| 5 |
| EG001 | Tamoxifen + Palbociclib | Tamoxifen: 20mg PO Q-daily Palbociclib: 125mg/day PO on a 21 days on/7 days off schedule | 1 | 2 | 0 | 2 | 2 | 2 |
| White blood cell decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blood and lymphatic system disorders - Other | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| General disorders and administration site conditions | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Renal and urinary disorders - Other | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Heart failure | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nervous system disorders - Other | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Psychiatric disorders - Other | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| 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 |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| Stable Disease (SD) |
|
| Progressive Disease (PD) |
|