Not provided
Not provided
Not provided
Not provided
Sufficient accrual into the African American/Black patient cohort and insufficient accrual into the NHW patient cohort.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Medstar Health Research Institute | OTHER |
| Breast Cancer Research Foundation | OTHER |
| Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) | OTHER |
Not provided
Not provided
Not provided
The aim is to determine the pharmacological and biochemical association between ribociclib exposure and CYP3A variants in African American/Blacks and Non-Hispanic White patients. The investigators hypothesize that patients treated with ribociclib who are CYP3A5 poor metabolizers may be exposed to higher levels of ribociclib than CYP3A5 intermediate or normal metabolizers. The findings could allow clinicians to tailor treatments to maintain therapeutic doses while limiting toxicities.
This prospective, multicenter, cohort study will assess ribociclib (600 mg PO daily) pharmacokinetics and pharmacogenomics in female patients with HR+/HER2- metastatic breast cancer. This design will be used for two independent, race-based cohorts: 18 African American/Black patients and 18 Non-Hispanic White patients. Women are eligible if they are older than 18, have HR+/HER2- mBC and are candidates for treatment with a CDK 4/6 inhibitor and endocrine therapy. Patients are ineligible if currently prescribed a medication that inhibits or induces the CYP3A isoenzymes, have baseline electrocardiogram abnormalities, or are otherwise considered to be ineligible for ribociclib. Participants will provide serial blood samples during the first cycle (collected immediately prior to the ribociclib dose, and 0.5hr ± 5min, 1hr ± 5min, 2hr ± 15min, 4hr ± 15min, 6hr ± 15min after the daily dose of ribociclib). Plasma samples will be analyzed via mass spectrometry to characterize the pharmacokinetics (e.g., AUC0-24, Cmax). Pharmacogenetic testing will be performed using the PharmacoScanTM microarray, which tests 4,627 markers in 1,191 genes, including variants in CYP3A4 and CYP3A5.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| African American/Black | Active Comparator | Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) |
|
| Non-Hispanic White | Active Comparator | Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ribociclib | Drug | Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
| Measure | Description | Time Frame |
|---|---|---|
| Ribociclib Area-under-the-curve (AUC) | Compare the exposure (i.e., AUC) of ribociclib at steady-state between CYP3A5 poor metabolizers (PM) and CYP3A5 intermediate or normal metabolizers (IM/NM) in each independent race-based cohort of women with advance breast cancer | On day 8-16 of cycle 1 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Ribociclib Pharmacokinetic Properties - Maximum Concentration (Cmax) | Maximum concentration (Cmax) at steady state between different CYP3A5 phenotypes | On day 8-16 of cycle 1 (each cycle is 28 days) |
| Ribociclib Pharmacokinetic Properties - the Time to Reach Cmax (Tmax) |
Not provided
Inclusion Criteria:
Signed informed consent must be obtained prior to any screening procedures.
Female ≥18 years old at the time of informed consent
Those who self-identify as African American or Black are eligible for that respective cohort
Those who self-identify as non-Hispanic White are eligible for that respective cohort
Postmenopausal or premenopausal. Patient has a known menopausal status at the time of the informed consent form signature. The patient is considered postmenopausal if: i) she has had prior bilateral oophorectomy; ii) is age ≥ 60 years; iii) is age <60 years and has had amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range per local normal ranges. All other patients who do not meet the criteria for postmenopausal status are considered premenopausal and will receive goserelin or leuprolide for ovarian suppression
Each race-based cohort has a predetermined number of patients with each CYP3A5 phenotype per the sample size calculation (section 9.1). Patients will be screen for CYP3A5: - African American or Black (At least 3 participants who are CYP3A5 poor metabolizers, No more than 15 participants who are CYP3A5 intermediate or normal metabolizers); - Non-Hispanic White (At least 3 participants who are CYP3A5 intermediate or normal metabolizers, No more than 15 participants who are CYP3A5 poor metabolizers)
Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy
Treated, stable and asymptomatic brain metastases are permitted
ECOG performance status 0-3
Documentation of estrogen receptor (ER) positive and/or progesterone receptor (PR) positive tumor (≥1% positive stained cells) based on most recent tumor biopsy (discuss with the Principal Investigator if results in different biopsies are discordant in terms of hormone receptor positivity) utilizing an assay consistent with local standards.
Documented HER2-negative tumor based on local testing on most recent tumor biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines. Patients with equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are eligible, as long as they have not received and are not scheduled to receive anti-HER2 treatment.
Must be capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the IRB, prior to the initiation of any screening or study-specific procedures.
Patient must be able to swallow ribociclib tablets.
Patient must be able to communicate with the investigator and comply with the requirements of the study procedures.
Patient has adequate bone marrow and organ function as defined by the following laboratory values:
Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements, or are not clinically significant per the Investigator
The following tests are not necessary. However, if results are available, values should be as follows:
Standard 12-lead electrocardiogram values defined as (obtained from baseline electrocardiogram):
Exclusion Criteria:
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.
Patient currently prescribed a CDK4/6 inhibitor (e.g., ribociclib, abemaciclib, or palbociclib).
Patients with central nervous system (CNS) symptomatic or untreated metastases
History of liver transplant or allogeneic bone marrow transplantation
Patient with a known hypersensitivity to any of the excipients of ribociclib (e.g. ribociclib tablets coating contains soya lecithin, and therefore should not be taken by patients who are allergic to peanuts or soya) or of fulvestrant.
Patient is concurrently using other anti-cancer therapy besides those in the study protocol (e.g., letrozole, fulvestrant, goserelin, leuprolide). Any other prior neo-/adjuvant anti-cancer therapy must be stopped at least 5 half-lives or 7 days, whichever is longer, before the date of ribociclib initiation.
Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities
Patient has not recovered from acute clinical and laboratory toxicities related to prior anticancer therapies to NCI CTCAE v5.0 grade ≤ 1 (except for alopecia, neuropathy, and amenorrhea or other toxicities not considered a safety risk for the patient at investigator's discretion).
Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to ribociclib initiation and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
Patient has a concurrent malignancy, with the exception of adequately treated basal or squamous cell skin carcinoma, stage 1 melanoma, or curatively resected cervical carcinoma in situ. Patients may still enroll with a concurrent malignancy after receiving approval from the study PI.
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drug (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
Patient has any other concurrent severe and/or uncontrolled medical condition that would in the investigator's judgment, cause unacceptable safety risks to the patient, contraindicate patient participation in the clinical study, or compromise compliance with the protocol.
Patient has clinically significant, uncontrolled heart disease or who are at significant risk of developing QT prolongation, including any of the following:
Patient is currently receiving any of the following substances and cannot be discontinued 7 days prior to Cycle 1 Day 1:
Concomitant medications, herbal supplements, and/or fruits that are strong inducers or inhibitors of CYP3A4/5.
Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
Chronic dosing of corticosteroids such as dexamethasone and prednisone is known to lead to induction of CYP3A enzymes, thereby potentially reducing ribociclib drug exposure to sub-therapeutic levels. Systemic corticosteroid treatment should not be given during the study treatment with ribociclib, except for:
Inability to comply with study requirements.
Psychiatric illness or social situation that would limit compliance with study requirements.
Patients with clinically significant liver disease, including active viral or other known hepatitis, current alcohol abuse, or cirrhosis.
Known active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg]) or known active hepatitis C (defined as a positive test for hepatitis C viral load by polymerase chain reaction [PCR]).
Known uncontrolled HIV infection defined as any of the following 3 criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Sandra Swain, MD | Georgetown University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MedStar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States | ||
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | African American/Black | Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
| FG001 | Non-Hispanic White | Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | African American/Black | Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
| 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 | Ribociclib Area-under-the-curve (AUC) | Compare the exposure (i.e., AUC) of ribociclib at steady-state between CYP3A5 poor metabolizers (PM) and CYP3A5 intermediate or normal metabolizers (IM/NM) in each independent race-based cohort of women with advance breast cancer | One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group. | Posted | Median | Inter-Quartile Range | hr*ng/mL | On day 8-16 of cycle 1 (each cycle is 28 days) |
|
29 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | African American/Black | Subject who self identify as African American or Black with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | CTCAE (5.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sandra Swain, MD, | Georgetown University | (202) 687-8487 | sandra.swain@georgetown.edu |
Not provided
| 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 | Sep 28, 2023 | Oct 23, 2024 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000589651 | ribociclib |
Not provided
Not provided
Not provided
| National Cancer Institute (NCI) |
| NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
the time to reach Cmax (Tmax) at steady state between different CYP3A5 phenotypes |
| On day 8-16 of cycle 1 (each cycle is 28 days) |
| Ribociclib Pharmacokinetic Properties - Clearance | clearance at steady state between different CYP3A5 phenotypes | On day 8-16 of cycle 1 (each cycle is 28 days) |
| Ribociclib Pharmacokinetic Properties - Volume of Distribution(vd) | Volume of distribution(vd) at steady state between different CYP3A5 phenotypes | days 8-16 of cycle 1 (28 day cycle) |
| Ribociclib Pharmacokinetic Properties - Elimination Half-life | Elimination half-life (t1/2) at steady state between different CYP3A5 phenotypes | On day 8-16 of cycle 1 (each cycle is 28 days) |
| Change in QTc Interval | Change in QTc interval between 1) baseline and between days 8-16 of cycle 1 (midcycle), and 2) baseline and scheduled visit prior to initiation of cycle 2 (C2), between different CYP3A5 phenotypes. | Baseline, day 8-16 of cycle 1 and prior to cycle 2 (each cycle is 28 days) |
| Laboratory Abnormalities - Neutropenia | Occurrence of neutropenia | from baseilne through prior to cycle 2 (each cycle is 28 days) |
| Laboratory Abnormalities - Aspartate Aminotransferase (AST) | Occurrence of Laboratory abnormalities: AST | From Baseline through prior to cycle 2 (each cycle is 28 days) |
| Laboratory Abnormalities -Alanine Aminotransferase (ALT) | Occurrence of Laboratory abnormalities: ALT between between different CYP3A5 phenotypes. | From Baseline to prior to cycle 2 (each cycle is 28 days) |
| Medstar Washington Hospital Center |
| Washington D.C. |
| District of Columbia |
| 20010 |
| United States |
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| BG001 | Non-Hispanic White | Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
| BG002 | 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 |
|
| CYP3A5 phenotype | Count of Participants | Participants |
|
| OG001 | Non-Hispanic White | Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. |
|
|
| Secondary | Ribociclib Pharmacokinetic Properties - Maximum Concentration (Cmax) | Maximum concentration (Cmax) at steady state between different CYP3A5 phenotypes | One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group. | Posted | Median | Inter-Quartile Range | ng/mL | On day 8-16 of cycle 1 (each cycle is 28 days) |
|
|
|
| Secondary | Ribociclib Pharmacokinetic Properties - the Time to Reach Cmax (Tmax) | the time to reach Cmax (Tmax) at steady state between different CYP3A5 phenotypes | One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group. | Posted | Median | Inter-Quartile Range | hour | On day 8-16 of cycle 1 (each cycle is 28 days) |
|
|
|
| Secondary | Ribociclib Pharmacokinetic Properties - Clearance | clearance at steady state between different CYP3A5 phenotypes | One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group. | Posted | Median | Inter-Quartile Range | liter/hour | On day 8-16 of cycle 1 (each cycle is 28 days) |
|
|
|
| Secondary | Ribociclib Pharmacokinetic Properties - Volume of Distribution(vd) | Volume of distribution(vd) at steady state between different CYP3A5 phenotypes | One subject in the Non-Hispanic white arm was excluded due to prohibited medication. | Posted | Median | Inter-Quartile Range | Liters | days 8-16 of cycle 1 (28 day cycle) |
|
|
|
| Secondary | Ribociclib Pharmacokinetic Properties - Elimination Half-life | Elimination half-life (t1/2) at steady state between different CYP3A5 phenotypes | One subject in the Non-Hispanic white arm was excluded to prohibited medication. All Non-Hispanic white participants were in the CYP3A5 Poor Metabolizers (PM) group. | Posted | Median | Inter-Quartile Range | hour | On day 8-16 of cycle 1 (each cycle is 28 days) |
|
|
|
| Secondary | Change in QTc Interval | Change in QTc interval between 1) baseline and between days 8-16 of cycle 1 (midcycle), and 2) baseline and scheduled visit prior to initiation of cycle 2 (C2), between different CYP3A5 phenotypes. | One subject in the Non-Hispanic white arm was excluded to prohibited medication. | Posted | Median | Inter-Quartile Range | Change in ms | Baseline, day 8-16 of cycle 1 and prior to cycle 2 (each cycle is 28 days) |
|
|
|
| Secondary | Laboratory Abnormalities - Neutropenia | Occurrence of neutropenia | One subject in the Non-Hispanic white arm was excluded to prohibited medication. | Posted | Count of Participants | Participants | from baseilne through prior to cycle 2 (each cycle is 28 days) |
|
|
|
| Secondary | Laboratory Abnormalities - Aspartate Aminotransferase (AST) | Occurrence of Laboratory abnormalities: AST | One subject in the Non-Hispanic white arm was excluded to prohibited medication. | Posted | Count of Participants | Participants | From Baseline through prior to cycle 2 (each cycle is 28 days) |
|
|
|
| Secondary | Laboratory Abnormalities -Alanine Aminotransferase (ALT) | Occurrence of Laboratory abnormalities: ALT between between different CYP3A5 phenotypes. | One subject in the Non-Hispanic white arm was excluded to prohibited medication. | Posted | Count of Participants | Participants | From Baseline to prior to cycle 2 (each cycle is 28 days) |
|
|
|
| 0 |
| 14 |
| 2 |
| 14 |
| 14 |
| 14 |
| EG001 | Non-Hispanic White | Subjects who self-identify as non-Hispanic White with metastatic HR+/HER2- advanced breast cancer (estimate 3 participants who are CYP3A5 poor metabolizers and approximately 15 participants who are CYP3A5 intermediate or normal metabolizers) Ribociclib: Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib. | 0 | 3 | 0 | 3 | 3 | 3 |
| Alanine aminotransferase increased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| White blood cell decreased | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Neutrophil count decreased | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Platelet count decreased | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| White blood cell decreased | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment | mouth sores |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment |
|
| Gum infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Infections and infestations - Other, specify | Infections and infestations | CTCAE (5.0) | Systematic Assessment | COVID-19 |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hot flashes | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
|
| QTc Prolongation | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
Not provided
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| Cmax CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|
| MidCycle- CYP3A5 PM |
|
|
| Prior to C2- CYP3A5 IM/NM |
|
|
| Prior to C2- CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|
| CYP3A5 PM |
|
|