Breast Cancer, Neutropenia
Conditions
Brief summary
This is a randomized, double-blind and placebo controlled phase 3 study to evaluate the efficacy and safety of F-627 in women with stage II-IV breast cancer receiving chemotherapy treatment.
Detailed description
This is a randomized, multi-center, single dose, double-blind, placebo controlled phase III study of the efficacy and safety of once-per-cycle of F-627 in women with stage II-IV breast cancer who are receiving myelotoxic TA chemotherapy treatment (Taxotere (docetaxel) + Adriamycin(doxorubicin)). F-627 is designed to treat neutropenia, an abnormally low number of neutrophils (a type of white blood cell) in the blood. Neutropenia is often seen in cancer patients receiving myelotoxic chemotherapy. The primary objective of this study is to evaluate the efficacy and safety of single fixed dose of F-627 in breast cancer patients experiencing myelotoxic chemotherapy in comparison to placebo. F-627 or placebo is to be administered subcutaneously 24 hours after chemotherapy in each 21-day cycle of chemotherapy treatment (up to 4 cycles). Patients randomized to placebo arm will receive F-627 except in cycle 1. The primary endpoint will be the duration of grade 4 (severe) neutropenia - the number of days in which the patient has had an absolute neutrophil count (ANC \< 0.5 x 10\^9/L) observed in chemotherapy cycle 1.
Interventions
DRUGF-627
F-627 subcutaneous injection on Day 2 of TA chemotherapy cycles. TA chemotherapy treatments are part of standard-of-care and not the study
DRUGPlacebo
Placebo subcutaneous injection on Day 2 of the first TA chemotherapy cycle. TA chemotherapy treatments are part of standard-of-care and not the study.
Sponsors
EVIVE Biotechnology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Show evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial. 2. Females ≥ 18 years of age and \< 75 years of age. 3. Diagnosed with Stage II-IV breast cancer. 4. Subject is scheduled to undergo 4 cycles of TA chemotherapy (docetaxel, doxorubicin, 75, and 60 mg/m2, respectively). 5. ECOG Performance status of ≤ 2. 6. White Blood Cell count (WBC) ≥ 4.0 × 109/L, hemoglobin ≥ 11.5 g/dL and a platelet count ≥ 150 × 109/L. 7. Demonstrate adequate renal, hepatic function (Liver function tests (ALT, AST, alkaline phosphatase and total bilirubin)) should be less than 2.5x upper limits of normal (ULN). Serum creatinine should be less than 1.7x ULN. 8. All subjects must agree to use at least one of the following types of contraception: intrauterine device, implantable progesterone device, progesterone intramuscular injection, or oral contraceptive, which has been started at least one month prior to visit one and will continue for the duration of the trial. The contraceptive patch or condom use with spermicide is also acceptable forms of contraception as long as they will be used continually throughout the duration of the trial.
Exclusion criteria
1. Subject is \<18 or ≥ 75 years of age. 2. Disease progression has occurred while receiving a taxane regimen. 3. Subject has undergone radiation therapy within 4 weeks of enrollment. 4. Subject has undergone bone marrow or stem-cell transplantation. 5. Subject has a history of prior malignancy other than breast cancer that is NOT in remission. 6. Subjects that have used G-CSF or any other drug that may potentiate the release of neutrophils (i.e. lithium) within 6 weeks of the screening period are excluded. 7. Subject has had chemotherapy within 365 days of screening. 8. Subject has documented congestive heart failure, cardiomyopathy or myocardial infarction by clinical diagnosis, ECG test, or any other relevant test. 9. History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure. 10. Unwillingness to participate in the study. 11. Any underlying medical condition that, in the Investigator's opinion, would make the administration of study drug hazardous to the patient or that would obscure the interpretation of adverse events. 12. Receiving other investigational drugs or biologics within 1 month or five half lives of enrollment. 13. Any condition, which can cause splenomegaly. 14. Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease. 15. ALT, AST, alkaline phosphatase, total bilirubin ≥ 2.5 upper limit of normal. 16. Subject with active infection, or known to be infected with chronic active Hepatitis B within the last 1 year (unless shown at the time of study entry to be Hepatitis B antigen negative), or having any history of Hepatitis C. 17. Women who are pregnant or breast-feeding. 18. Subject known to be seropositive for HIV, or who have had an AIDS defining illness or a known immunodeficiency disorder. 19. Subject with a history of tuberculosis or exposure to tuberculosis. Patients that have received a prior chest X-ray for suspicion of tuberculosis are also excluded unless they have been confirmed to be PPD negative or they had latent tuberculosis that has been previously treated. 20. Subjects with Sickle Cell disease 21. Subjects with known hypersensitivity to E.coli derived proteins' pegfilgrastim' filgrastim, or any other component of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Duration in Days of Grade 4 (Severe) Neutropenia Observed in Chemotherapy Cycle 1 in Comparison to Placebo | The first of 4, 21 Day Chemotherapy Cycles, an average of 3 weeks | Subjects will be randomized to F-627 or Placebo at 2:1 ratio. About 24 hours after chemotherapy, subjects will either receive 20mg fixed dose F-627 or Placebo. The subject's absolute neutrophil count (ANC) will be monitored each day post chemotherapy administration until the ANC level exceeds 2.0x10\^9/L, then the value will be monitored every three days until the next chemotherapy cycle is entered. The duration of grade 4 neutropenia (ANC \<0.5x10\^9/L) in this cycle is the primary efficacy endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | 4 chemotherapy cycles, about 12 weeks | The duration in days of mild, moderate and severe neutropenia will be recorded for 4 chemotherapy cycles. Grade 2 neutropenia is when a patient's ANC\<1.5x10\^9/L, Grade 3 neutropenia is when a patient's ANC\<1.0x10\^9/L, and Grade 4 neutropenia is when a patient's ANC \<0.5x10\^9/L. |
| Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | 4 chemotherapy cycles, about 12 weeks | Febrile neutropenia is defined as a single oral temperature of ≥38.3°C (101°F) or a temperature of \>38.0°C (100.4°F) sustained for \>1 hour and ANC \< 0.5 x 10\^9/L |
| Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | 4 chemotherapy cycles, about 12 weeks | The number of subjects with grade 2, 3 and 4 neutropenia will be recorded for all 4 chemotherapy cycles. |
| The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Over all 4 cycles, about 12 weeks | The duration of severe neutropenia will be measured for each patient during chemotherapy cycle 2-4 and over all cycles. Each chemotherapy is expected to last 21 days. |
| The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | 4 chemotherapy cycles, about 12 weeks | The depth of ANC nadir for each cycle is the minimal ANC value (× 10\^9/L ) for a patient in each chemotherapy cycle |
| Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | 4 chemotherapy cycles, about 12 weeks | The number of subjects with infections for each arm of the study will be recorded for each and all 4 chemotherapy cycles. |
| Number of Participants With Use of Antibiotics and Pain Medications | 4 chemotherapy cycles, about 12 weeks | Antibiotics and pain medications use will be recorded for each chemotherapy cycle and overall cycles |
| The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | 4 chemotherapy cycles, about 12 weeks | The time to ANC recovery post nadir for each patient, for each of their chemotherapy cycles will be recorded. Recovery for this protocol is defined as achieving an ANC ≥ 2.0 × 10\^9/L after the expected ANC nadir (expected nadir is typically 4-6 days post chemotherapy administration). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| F-627 F-627, 20 mg fixed dose pre-filled syringe, dosed Day 2 of each of 4 chemotherapy cycles. | 83 |
| Placebo Placebo, pre-filled syringe administered Day 2 of the first chemotherapy cycle; and F-627, 20 mg fixed dose pre-filled syringe administered Day 2 of each of the following 3 chemotherapy cycles. | 39 |
| Total | 122 |
Baseline characteristics
| Characteristic | Placebo | F-627 | Total |
|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 9 | 50.8 years STANDARD_DEVIATION 9.25 | 51.0 years STANDARD_DEVIATION 9.14 |
| Baseline ECOG Grade 0 | 27 Participants | 46 Participants | 73 Participants |
| Baseline ECOG Grade 1 | 12 Participants | 37 Participants | 49 Participants |
| BMI (kg/m^2) | 27.4 kg/m^2 STANDARD_DEVIATION 6.22 | 26.2 kg/m^2 STANDARD_DEVIATION 5.36 | 26.6 kg/m^2 STANDARD_DEVIATION 5.65 |
| Cancer Stage at Screening Stage II | 21 Participants | 43 Participants | 64 Participants |
| Cancer Stage at Screening Stage III | 12 Participants | 22 Participants | 34 Participants |
| Cancer Stage at Screening Stage IV | 6 Participants | 18 Participants | 24 Participants |
| Days from Diagnosis | 445.9 days STANDARD_DEVIATION 1337.99 | 224.5 days STANDARD_DEVIATION 572.21 | 294.6 days STANDARD_DEVIATION 888.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 82 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 82 Participants | 121 Participants |
| Region of Enrollment Hungary | 1 participants | 4 participants | 5 participants |
| Region of Enrollment Russia | 16 participants | 32 participants | 48 participants |
| Region of Enrollment Ukraine | 22 participants | 46 participants | 68 participants |
| Region of Enrollment United States | 0 participants | 1 participants | 1 participants |
| Reproductive Status Childbearing potential | 15 Participants | 37 Participants | 52 Participants |
| Reproductive Status Non-childbearing potential - Post-menopausal | 23 Participants | 42 Participants | 65 Participants |
| Reproductive Status Non-childbearing potential - Surgically sterile | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 39 Participants | 83 Participants | 122 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 39 | 0 / 83 | 0 / 39 |
| other Total, other adverse events | 17 / 83 | 5 / 39 | 26 / 83 | 9 / 39 |
| serious Total, serious adverse events | 4 / 83 | 10 / 39 | 4 / 83 | 11 / 39 |
Outcome results
Primary
The Duration in Days of Grade 4 (Severe) Neutropenia Observed in Chemotherapy Cycle 1 in Comparison to Placebo
Subjects will be randomized to F-627 or Placebo at 2:1 ratio. About 24 hours after chemotherapy, subjects will either receive 20mg fixed dose F-627 or Placebo. The subject's absolute neutrophil count (ANC) will be monitored each day post chemotherapy administration until the ANC level exceeds 2.0x10\^9/L, then the value will be monitored every three days until the next chemotherapy cycle is entered. The duration of grade 4 neutropenia (ANC \<0.5x10\^9/L) in this cycle is the primary efficacy endpoint.
Time frame: The first of 4, 21 Day Chemotherapy Cycles, an average of 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F-627 | The Duration in Days of Grade 4 (Severe) Neutropenia Observed in Chemotherapy Cycle 1 in Comparison to Placebo | 1.3 days | Standard Deviation 1.17 |
| Placebo | The Duration in Days of Grade 4 (Severe) Neutropenia Observed in Chemotherapy Cycle 1 in Comparison to Placebo | 3.9 days | Standard Deviation 1.35 |
Secondary
Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles
Febrile neutropenia is defined as a single oral temperature of ≥38.3°C (101°F) or a temperature of \>38.0°C (100.4°F) sustained for \>1 hour and ANC \< 0.5 x 10\^9/L
Time frame: 4 chemotherapy cycles, about 12 weeks
Population: 3 subjects terminated early.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 2 | Subjects with FN | 0 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 3 | Subject without FN | 82 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 1 | Subject without FN | 79 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 4 | Subjects with FN | 0 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 2 | Subject without FN | 83 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 1 | Subjects with FN | 4 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | All cycles | Subjects with FN | 4 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 3 | Subjects with FN | 0 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | All cycles | Subject without FN | 79 Participants |
| F-627 | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 4 | Subject without FN | 82 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | All cycles | Subject without FN | 28 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 1 | Subjects with FN | 10 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 1 | Subject without FN | 29 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 2 | Subjects with FN | 1 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 2 | Subject without FN | 37 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 3 | Subjects with FN | 0 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 3 | Subject without FN | 37 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 4 | Subjects with FN | 0 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | Cycle 4 | Subject without FN | 37 Participants |
| Placebo | Number of Participants With Febrile Neutropenia (FN) for Each Chemotherapy Cycle and Over All Cycles | All cycles | Subjects with FN | 11 Participants |
Secondary
Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles.
The number of subjects with grade 2, 3 and 4 neutropenia will be recorded for all 4 chemotherapy cycles.
Time frame: 4 chemotherapy cycles, about 12 weeks
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| F-627 | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 4 Neutropenia | yes | 58 Participants |
| F-627 | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 4 Neutropenia | no | 25 Participants |
| F-627 | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 3 Neutropenia | yes | 71 Participants |
| F-627 | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 3 Neutropenia | no | 12 Participants |
| F-627 | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 2 Neutropenia | yes | 77 Participants |
| F-627 | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 2 Neutropenia | no | 6 Participants |
| Placebo | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 2 Neutropenia | yes | 37 Participants |
| Placebo | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 4 Neutropenia | yes | 37 Participants |
| Placebo | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 3 Neutropenia | no | 2 Participants |
| Placebo | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 4 Neutropenia | no | 2 Participants |
| Placebo | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 2 Neutropenia | no | 2 Participants |
| Placebo | Number of Participants With Grade 2, Grade 3, and Grade 4 Neutropenia for All Chemotherapy Cycles. | Grade 3 Neutropenia | yes | 37 Participants |
Secondary
Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles.
The number of subjects with infections for each arm of the study will be recorded for each and all 4 chemotherapy cycles.
Time frame: 4 chemotherapy cycles, about 12 weeks
Population: Some subjects terminated earlier
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 2 | Subjects with infection | 1 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 3 | Subjects without infection | 77 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 1 | Subjects without infection | 81 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 2 | Subjects without infection | 82 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 4 | Subjects without infection | 81 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 1 | Subjects with infection | 2 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | All cycles | Subjects with infection | 9 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 3 | Subjects with infection | 5 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | All cycles | Subjects without infection | 74 Participants |
| F-627 | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 4 | Subjects with infection | 1 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | All cycles | Subjects without infection | 31 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 1 | Subjects with infection | 3 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 1 | Subjects without infection | 36 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 2 | Subjects with infection | 2 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 2 | Subjects without infection | 36 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 3 | Subjects with infection | 3 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 3 | Subjects without infection | 34 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 4 | Subjects with infection | 0 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | Cycle 4 | Subjects without infection | 37 Participants |
| Placebo | Number of Participants With Infections for Each Chemotherapy Cycle and Over All Cycles. | All cycles | Subjects with infection | 8 Participants |
Secondary
Number of Participants With Use of Antibiotics and Pain Medications
Antibiotics and pain medications use will be recorded for each chemotherapy cycle and overall cycles
Time frame: 4 chemotherapy cycles, about 12 weeks
Population: 3 subjects terminated early
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 1 | antibiotic and pain medications use | 9 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 1 | no antibiotic and pain medications use | 74 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 2 | antibiotic and pain medications use | 3 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 2 | no antibiotic and pain medications use | 80 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 3 | antibiotic and pain medications use | 2 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 3 | no antibiotic and pain medications use | 80 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 4 | antibiotic and pain medications use | 1 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 4 | no antibiotic and pain medications use | 81 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | All cycles | antibiotic and pain medications use | 13 Participants |
| F-627 | Number of Participants With Use of Antibiotics and Pain Medications | All cycles | no antibiotic and pain medications use | 70 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 4 | no antibiotic and pain medications use | 37 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 1 | antibiotic and pain medications use | 13 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 3 | no antibiotic and pain medications use | 36 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 1 | no antibiotic and pain medications use | 26 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | All cycles | no antibiotic and pain medications use | 24 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 2 | antibiotic and pain medications use | 2 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 4 | antibiotic and pain medications use | 0 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 2 | no antibiotic and pain medications use | 36 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | All cycles | antibiotic and pain medications use | 15 Participants |
| Placebo | Number of Participants With Use of Antibiotics and Pain Medications | Cycle 3 | antibiotic and pain medications use | 1 Participants |
Secondary
The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles.
The depth of ANC nadir for each cycle is the minimal ANC value (× 10\^9/L ) for a patient in each chemotherapy cycle
Time frame: 4 chemotherapy cycles, about 12 weeks
Population: 3 subjects terminated early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 2 | 2.0 cells/10^9/L | Standard Deviation 1.71 |
| F-627 | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 4 | 1.7 cells/10^9/L | Standard Deviation 1.45 |
| F-627 | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 3 | 1.7 cells/10^9/L | Standard Deviation 1.58 |
| F-627 | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | All cycles | 1.5 cells/10^9/L | Standard Deviation 1.2 |
| F-627 | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 1 | 0.7 cells/10^9/L | Standard Deviation 1.16 |
| Placebo | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | All cycles | 1.4 cells/10^9/L | Standard Deviation 1.23 |
| Placebo | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 1 | 0.2 cells/10^9/L | Standard Deviation 0.57 |
| Placebo | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 2 | 1.6 cells/10^9/L | Standard Deviation 1.71 |
| Placebo | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 3 | 1.8 cells/10^9/L | Standard Deviation 1.63 |
| Placebo | The Depth of the ANC Nadir for Each Chemotherapy Cycle and Over All Cycles. | Cycle 4 | 2.3 cells/10^9/L | Standard Deviation 2.01 |
Secondary
The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles.
The duration in days of mild, moderate and severe neutropenia will be recorded for 4 chemotherapy cycles. Grade 2 neutropenia is when a patient's ANC\<1.5x10\^9/L, Grade 3 neutropenia is when a patient's ANC\<1.0x10\^9/L, and Grade 4 neutropenia is when a patient's ANC \<0.5x10\^9/L.
Time frame: 4 chemotherapy cycles, about 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 | The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | Grade 4 | 0.5 days | Standard Deviation 0.62 |
| F-627 | The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | Grade 3 | 1.2 days | Standard Deviation 1.08 |
| F-627 | The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | Grade 2 | 1.8 days | Standard Deviation 1.24 |
| Placebo | The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | Grade 4 | 1.4 days | Standard Deviation 1.32 |
| Placebo | The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | Grade 3 | 1.9 days | Standard Deviation 1.46 |
| Placebo | The Duration in Days of Grade 2 (Mild), Grade 3 (Moderate) and 4 (Severe) Neutropenia Over All Cycles. | Grade 2 | 2.7 days | Standard Deviation 1.71 |
Secondary
The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles.
The duration of severe neutropenia will be measured for each patient during chemotherapy cycle 2-4 and over all cycles. Each chemotherapy is expected to last 21 days.
Time frame: Over all 4 cycles, about 12 weeks
Population: Missing ANC data. No multiple imputation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Cycle 2 | 0.3 days | Standard Deviation 0.76 |
| F-627 | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Cycle 3 | 0.3 days | Standard Deviation 0.84 |
| F-627 | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Cycle 4 | 0.2 days | Standard Deviation 0.62 |
| F-627 | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | All cycles | 0.5 days | Standard Deviation 0.62 |
| Placebo | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | All cycles | 1.4 days | Standard Deviation 1.32 |
| Placebo | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Cycle 2 | 0.8 days | Standard Deviation 1.2 |
| Placebo | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Cycle 4 | 0.7 days | Standard Deviation 1.39 |
| Placebo | The Duration in Days of Grade 4 (Severe) Neutropenia (ANC < 0.5 × 10^9/L) for Chemotherapy Cycles 2, 3, and 4, and Over All Cycles. | Cycle 3 | 0.5 days | Standard Deviation 1.19 |
Secondary
The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir.
The time to ANC recovery post nadir for each patient, for each of their chemotherapy cycles will be recorded. Recovery for this protocol is defined as achieving an ANC ≥ 2.0 × 10\^9/L after the expected ANC nadir (expected nadir is typically 4-6 days post chemotherapy administration).
Time frame: 4 chemotherapy cycles, about 12 weeks
Population: 3 Subjects terminated early (1 in F-627 arm, 2 in the placebo arm). In addition, 1 subject in placebo arm reached her Nadir(1.81) at Day 7 but the rest of ANC values are missing. Because the recovery information is not available, this subject was removed from the Time to ANC recovery analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 2 | 1.6 days | Standard Deviation 1.35 |
| F-627 | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 4 | 1.9 days | Standard Deviation 1.39 |
| F-627 | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 3 | 1.6 days | Standard Deviation 1.34 |
| F-627 | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | All cycles | 1.8 days | Standard Deviation 0.94 |
| F-627 | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 1 | 2.1 days | Standard Deviation 1.08 |
| Placebo | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | All cycles | 2.4 days | Standard Deviation 1.2 |
| Placebo | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 1 | 4.0 days | Standard Deviation 2.07 |
| Placebo | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 2 | 2.0 days | Standard Deviation 1.37 |
| Placebo | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 3 | 1.7 days | Standard Deviation 1.79 |
| Placebo | The Time in Days to ANC Recovery Post Nadir for Each Chemotherapy Cycle and Over All Cycles; Recovery Defined as an ANC ≥ 2.0 × 10^9/L After the Expected ANC Nadir. | Cycle 4 | 1.5 days | Standard Deviation 1.73 |