Breast Cancer, Estrogen Receptor Positive Tumor
Conditions
Keywords
Estrogen Receptor-Positive Early Stage Breast Cancer
Brief summary
This is a Phase 2, multicenter, single-arm, feasibility study evaluating eribulin in combination with capecitabine as an adjuvant chemotherapy regimen in approximately 65 subjects with early-stage (I-II), human epidermal growth factor receptor 2 (HER2)- normal, estrogen receptor (ER)-positive breast cancer.
Interventions
DRUGeribulin mesylate
Cohort I & II: eribulin mesylate (E7389) 1.4 mg/m2 intravenously over 2 - 5 minutes on Day 1 and Day 8 for 4 cycles
DRUGcapecitabine
Cohort 1: capecitabine 900 mg/m2 orally twice daily on Days 1 - 14 of a 21-day cycle for 4 cycles Cohort II: fixed dose of 1500 mg oral capecitabine twice daily, 7 days on then 7 days off for 4 cycles
Sponsors
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male subjects aged greater than or equal to 18 years and female subjects who must be postmenopausal (at least 12 months consecutive amenorrheic or have had a bilateral oophorectomy or, if they have had a hysterectomy but with ovaries intact, then females must be age 55 or older and with postmenopausal follicle-stimulating hormone \[FSH\] levels). 2. Subject is a candidate for chemotherapy in the adjuvant setting. * Adjuvant therapy must begin within 84 days of the final surgical procedure for breast cancer. 3. Histologically confirmed Stage I to II invasive breast cancer. Subjects may have more than one synchronous primary breast tumor. 4. Receptor Status: * HER2-normal as determined by a negative fluorescence in situ hybridization (FISH) result or 0 to 1+ by immunohistochemistry (IHC) staining result * ER-positive, node-negative or ER-positive Grade 1 or 2 node-positive breast cancer 5. ECOG performance status of 0 or 1 6. Adequate renal function as evidenced by serum creatinine less than or equal to 1.5 mg/dL or calculated creatinine clearance greater than or equal to 50 mL/min per the Cockcroft and Gault formula 7. Adequate bone marrow function as evidenced by ANC greater than or equal to 1.5 x 10\^9/L, hemoglobin greater than or equal to 10.0 g/dL, and platelet count greater than or equal to 100 x 10\^9/L 8. Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN 9. Male subjects must have had a successful vasectomy (confirmed azoospermia), or their female partners must not be of childbearing potential, or male subjects must agree to use and have their female partners use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\] throughout the entire study period and for 30 days after study drug discontinuation.. 10. Voluntary agreement to provide written informed consent and willingness and ability to comply with all aspects of the protocol
Exclusion criteria
1. Stage III and IV invasive breast cancer 2. Prior chemotherapy, radiation therapy, immunotherapy or biotherapy for current breast cancer 3. Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc) that would preclude any of the study therapy drugs 4. Subjects with a concurrently active second malignancy other than adequately treated nonmelanoma skin cancers or in situ cervical cancer 5. Subjects with pre-existing neuropathy greater than Grade 2 6. Subjects with known positive human immunodeficiency virus (HIV) status 7. Females of childbearing potential. Females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic or have had a bilateral oophorectomy or, if they have had a hysterectomy but with ovaries intact, then females must be age 55 or older and with postmenopausal FSH levels). 8. Subjects with current gastrointestinal disease or other condition resulting in an inability to take or absorb oral medications 9. Subjects with known allergy or hypersensitivity to eribulin mesylate or its excipients, or to fluoropyrimidine therapy (with or without documented dihydropyrimidine dehydrogenase \[DPD\] deficiency) 10. A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolongation of QT/QTc interval (time between the start of the Q wave and the end of the T wave/QT interval corrected for heart rate) (e.g., repeated demonstration of a QTc interval greater than 500 ms) 11. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved the Target Relative Dose Intensity (RDI) of 85% | 21-Day Cycle 1 through 21-Day Cycle 4 | Relative Dose Intensity (RDI) is defined as the amount of drug administered over a specific time and is expressed as the fraction of that recommended for standard of care. The RDI for each participant was calculated as follows: (1) based on each participant's body surface area (BSA), a total planned dose for both eribulin (Dep) and capecitabine (Dcp) calculated for a full 4-cycle regimen; (2) actual total dose of eribulin (Dea) and capecitabine (Dca) for the full 4-cycle regimen as collected on the case report form; (3) overall RDI = (Dea/Dep + Dca/Dcp)/2. For each individual participant, the regimen was considered feasible if that participant was able to achieve an RDI of at least 85% of the 4 cycles of eribulin plus capecitabine treatment. Missing doses due to any reason was counted as zero in the RDI calculation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Use of Cold Cap for Alopecia | On the day of study drug infusion treatments during Cycles 1 through 4 | Alopecia (hair loss) is a potential side effect of some chemotherapy agents. Chemotherapeutic drugs are toxic and could potentially harm the hair follicles (wear hair grows from) resulting in the hair falling out. It can occur in small patches on various parts of the body or all over the body and is usually temporary when related to cancer treatment. Cold cap therapy is one form of therapy for alopecia involving hair loss from the scalp. Wearing a cap or head covering with cold packs before, during, or after chemotherapy may help prevent hair loss as the cold narrows the blood vessels in the skin on your head which may lead to less of the drug reaching the hair follicles. Alopecia was one of the most common adverse events (AEs) related to eribulin only. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Day 1 through 30 days after last dose of study drugs (approximately up to 3 years) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine Eribulin mesylate (1.4 mg/m\^2) was injected directly as an IV infusion over 2 to 5 minutes on Day 1 and Day 8 of the 21-day cycle for a total of 4 cycles. Alternatively, eribulin mesylate could be diluted in up to 100 mL in 0.9% sodium chloride for IV infusion over 2 to 5 minutes. Capecitabine (900 mg/m\^2) was administered orally BID on Days 1 through 14 of a 21-day cycle for a total of 4 cycles. Capecitabine was to be taken approximately 30 minutes after breakfast and approximately 30 minutes after dinner. | 67 |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine Eribulin mesylate (E7389) (1.4 mg/m\^2) was injected directly as an IV infusion over 2 to 5 minutes on Day 1 and Day 8 of the 21-day cycle for a total of 4 cycles. Alternatively, eribulin mesylate could be diluted in up to 100 mL in 0.9% sodium chloride for IV infusion over 2 to 5 minutes. A fixed dose of capecitabine (1500 mg) was administered orally BID on a 7/7 schedule (7days on and 7 days off) for a total of 4 cycles. Capecitabine was to be taken approximately 30 minutes after breakfast and approximately 30 minutes after dinner. | 10 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 3 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 7 Participants | 53 Participants |
| Sex: Female, Male Female | 67 Participants | 10 Participants | 77 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 67 | 10 / 10 |
| serious Total, serious adverse events | 14 / 67 | 1 / 10 |
Outcome results
Primary
Percentage of Participants Who Achieved the Target Relative Dose Intensity (RDI) of 85%
Relative Dose Intensity (RDI) is defined as the amount of drug administered over a specific time and is expressed as the fraction of that recommended for standard of care. The RDI for each participant was calculated as follows: (1) based on each participant's body surface area (BSA), a total planned dose for both eribulin (Dep) and capecitabine (Dcp) calculated for a full 4-cycle regimen; (2) actual total dose of eribulin (Dea) and capecitabine (Dca) for the full 4-cycle regimen as collected on the case report form; (3) overall RDI = (Dea/Dep + Dca/Dcp)/2. For each individual participant, the regimen was considered feasible if that participant was able to achieve an RDI of at least 85% of the 4 cycles of eribulin plus capecitabine treatment. Missing doses due to any reason was counted as zero in the RDI calculation.
Time frame: 21-Day Cycle 1 through 21-Day Cycle 4
Population: Full analysis set included all participants who received at least one dose of eribulin mesylate plus capecitabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Percentage of Participants Who Achieved the Target Relative Dose Intensity (RDI) of 85% | 77.6 Percentage of participants |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Percentage of Participants Who Achieved the Target Relative Dose Intensity (RDI) of 85% | 90.0 Percentage of participants |
p-value: 0.1081-sample binomial test
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 through 30 days after last dose of study drugs (approximately up to 3 years)
Population: The safety analysis set was all participants who received at least 1 dose of study treatments and had at least 1 post treatment safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 67 participants |
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 14 participants |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 10 participants |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 1 participants |
Secondary
Use of Cold Cap for Alopecia
Alopecia (hair loss) is a potential side effect of some chemotherapy agents. Chemotherapeutic drugs are toxic and could potentially harm the hair follicles (wear hair grows from) resulting in the hair falling out. It can occur in small patches on various parts of the body or all over the body and is usually temporary when related to cancer treatment. Cold cap therapy is one form of therapy for alopecia involving hair loss from the scalp. Wearing a cap or head covering with cold packs before, during, or after chemotherapy may help prevent hair loss as the cold narrows the blood vessels in the skin on your head which may lead to less of the drug reaching the hair follicles. Alopecia was one of the most common adverse events (AEs) related to eribulin only.
Time frame: On the day of study drug infusion treatments during Cycles 1 through 4
Population: Safety analysis set included all participants who received at least one dose of study treatments and had at least one postbaseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Use of Cold Cap for Alopecia | Participants with alopecia | 52 Participants |
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Use of Cold Cap for Alopecia | Participants who used a cold cap | 3 Participants |
| Cohort 1: Eribulin Mesylate Plus 900 mg/m^2 Capecitabine | Use of Cold Cap for Alopecia | Participants who did not use a cold cap | 49 Participants |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Use of Cold Cap for Alopecia | Participants with alopecia | 9 Participants |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Use of Cold Cap for Alopecia | Participants who used a cold cap | 0 Participants |
| Cohort 2: Eribulin Mesylate Plus 1500 mg Capecitabine | Use of Cold Cap for Alopecia | Participants who did not use a cold cap | 9 Participants |