Early Stage Breast Cancer
Conditions
Keywords
Early Stage Breast Cancer
Brief summary
This research study is testing the safety and feasibility of delivering the 4 cycles of 'dose-dense' paclitaxel without the use of Neulasta (Pegfilgrastim) as a Granulocyte Colony-stimulating Factor (G-CSF) support. The research study is for participants who have early stage breast cancer and have been recommended to receive a standard chemotherapy regimen, doxorubicin/cyclophosphamide (AC) plus Paclitaxel (T), in what is called a dose-dense fashion to prevent recurrences.
Detailed description
Low white cell blood counts increase the risk of infections; thus, in order to give each cycle of chemotherapy, white blood cell count must have recovered adequately in between cycles. Traditionally, this regimen has been given with the use of a medicine called Neulasta (Pegfilgrastim) to speed the recovery of the white blood cell count in order to maximize the chances that the next cycle of chemotherapy can be given on time. The names of the study interventions involved in this study are: \-- Neulasta (Pegfilgrastim)
Interventions
DRUGPaclitaxel
DRUGNeulasta
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically confirmed Stage I-III breast cancer (as defined by the revised, American Joint Committee on Cancer 7th edition criteria) and be at sufficient risk for tumor recurrence. Staging studies to exclude metastatic disease are not required in asymptomatic patients. However, patients with findings considered suspicious for metastatic disease on any staging studies that are obtained need to be evaluated to exclude stage IV breast cancer. * Patients must be deemed by their treating oncologist as candidates for (neo) adjuvant chemotherapy with dose dense AC and T. * Age ≥ 18 years and \< 65 at the time of informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. * Any grade 3 or clinically significant grade 2 treatment-related non-hematological toxicity must be resolved to grade 1 before retreatment with chemotherapy (with exception of alopecia) * Laboratory Evaluations: * Adequate blood marrow function defined as: * Absolute neutrophil count (ANC) ≥1500 µL * Hemoglobin ≥9.0 g/dl * Platelets ≥100,000/mm3 * Adequate hepatic function defined as: * Total bilirubin ≤ 1.2 institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase ≤ 1.5 X upper limit normal (ULN) * Adequate renal function defined as: \--- Serum creatinine ≤ 1.5 X ULN * Premenopausal women (including women who have had a tubal ligation and for women less than 12 months after the onset of menopause) must have a negative serum pregnancy test. * Patients with risk factors for Hepatitis B or C should be tested (anti-hepatitis C virus (HCV) antibody, hepatitis B surface antigen \[HBsAg\] or Hepatitis B core antibody). Risk factors include: history of unprotected sexual intercourse, intravenous drug use, or originally from endemic regions. If infection is suspected, hepatitis B virus (HBV) DNA and HCV RNA should be requested as appropriate. * Note: Patients with positive Hepatitis B or C serologies without known active disease must meet the eligibility requirements for ALT, AST, total bilirubin, and alkaline phosphatase and must have a normal international normalized ratio (INR) on at least two consecutive occasions, separated by at least 1 week, within the 30 day screening period. * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patients who have received previous cytotoxic chemotherapy including an AC-T regimen or previous therapeutic radiation therapy for any reason in the last 5 years. Because of possible limitations in bone marrow reserve, patients with such prior treatments are not appropriate candidates for this trial. Patients who have had prior hormonal therapy (for instance, tamoxifen for prevention of breast cancer) are eligible. Patients who have participated in a window study (treatment with an investigational agent prior to surgery for ≤2 weeks) are eligible but must have discontinued the investigational agent at least 14 days before enrollment. * Participants who are receiving any other investigational agents * Have had at least one prior episode of fever and neutropenia (ANC\< 500/mm3 or expected to fall below \< 500/mm3) during AC. * Patients taking lithium. * Patients receiving chronic treatment with oral steroids or another immunosuppressive agent (excluding steroids as part of the chemotherapy pre-medication or emetic medication). * Known HIV-positive individuals or with any immunodeficiency status. * Patients with history of hematologic disease, including myelodysplasia or bone marrow malignancies. * History of allergic reaction attributed to compounds of similar chemical or biologic composition to Paclitaxel, which cannot be managed by premedication. * Currently pregnant or breast-feeding. * Uncontrolled intercurrent illness including, not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or other significant diseases or disorders that, in the investigator's opinion, would exclude the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Paclitaxel Treatment Completion Within 7 Weeks | 7 Weeks | Rate of participants who completed Paclitaxel treatment in 7 weeks while omitting Neulasta™ (Pegfilgrastim). Neulasta is administered based on the following pre-specified safety criteria. * The patient experiences a prior episode of fever and neutropenia. * If the patient has an active infection this decision will be at provider discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Grade 3-4 Toxicities, Excluding Neutropenia | While on study, up to 6.2 months | Percentage of participants experiencing a grade 3 or 4 toxicity excluding grade 3 or 4 neutropenia or febrile neutropenia per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
| Rate of Chemotherapy Dose Reductions | While on treatment, up to 2.3 months | Percentage of participants experiencing dose reductions due to adverse events. |
| Percentage of Participants Who Received All Planned Chemotherapy Cycles | While on treatment, up to 2.3 months | Percentage of Participants who received all planned chemotherapy cycles. |
| Rate of Grade 3-5 Neutropenia | While on study, up to 6.2 months | Percentage of participants experiencing grade 3-5 neutropenia per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. while on treatment. |
| Number of Participants With Dose Delays by Reason for Delay | While on treatment, up to 2.3 months | Number of participants with dose delays due to various different adverse events. Adverse events classified using CTCAEv 4.0. |
| Median of Savings When Omitting Pegfilgrastim From Treatment. | While on treatment, up to 2.3 months | An algorithm was used to estimated median and range of potential savings per 100 patients if the use of pegfilgrastim was omitted from treatment. The algorithm is designed assuming an average wholesale price in the United States ranging from $1,361 to $4,655 for myeloid growth factors such as filgrastim (8 days of growth factor support/cycle) and peg-filgrastim ($5,443 to $18,622 for 4 cycles on the basis of April 2019 Medicare Part B Drug Average Sales Price), and applying a 95.7% reduction in the use of pegfilgrastim during paclitaxel. |
| Rate of Hypersensitivity Reactions on Cycles 3-4 of Paclitaxel, When Steroid is Avoided | While on treatment, up to 2.3 months | The percentage of participants who experienced a hypersensitivity reaction on cycles 3 and 4 without use of dexamethasone (a steroid).. |
Countries
United States
Participant flow
Recruitment details
Enrollment Period: May 2016 and November 2018
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel After the screening procedures confirm participation in the research study:
175 mg/m\^2 Paclitaxel via IV, once every 2 weeks x 4 cycles. (1 cycle = 2 weeks)
\-- Neulasta™ (Pegfilgrastim) 6 mg SQ x1 is administered on day 2 of each treatment cycle, approximately 24 hours after the chemotherapy treatment, if:
* The patient experiences a prior episode of fever and neutropenia.
* If the patient has an active infection this decision will be at provider discretion.
* If Neulasta™(Pegfilgrastim) is administered in any Paclitaxel cycle for a given patient, it will be then administered for all future cycles.
Paclitaxel
Neulasta | 125 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | deemed ineligible | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Paclitaxel |
|---|---|
| Age, Continuous | 46 years |
| Body Surface Area | 1.81 m^2 |
| Chemotherapy Setting Adjuvant | 68 Participants |
| Chemotherapy Setting Neoadjuvant | 57 Participants |
| ECOG Performance Status 0 - Fully Active | 119 Participants |
| ECOG Performance Status 1 - Restricted | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 113 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Histology Ductal Carcinoma | 94 Participants |
| Histology Lobular Carcinoma | 16 Participants |
| Histology Mixed Lobular and Ductal Carcinoma | 13 Participants |
| Histology Other | 2 Participants |
| Hormone Receptor Status Estrogen and Progesterone Receptor Negative | 44 Participants |
| Hormone Receptor Status Estrogen and Progesterone Receptor Positive | 80 Participants |
| Hormone Receptor Status Unknown | 1 Participants |
| Menopausal Status Postmenopausal | 41 Participants |
| Menopausal Status Premenopausal | 84 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) White | 101 Participants |
| Sex: Female, Male Female | 125 Participants |
| Sex: Female, Male Male | 0 Participants |
| Stage at Initial Diagnosis Stage I | 16 Participants |
| Stage at Initial Diagnosis Stage II | 81 Participants |
| Stage at Initial Diagnosis Stage III | 27 Participants |
| Stage at Initial Diagnosis Unknown | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 127 |
| other Total, other adverse events | 63 / 127 |
| serious Total, serious adverse events | 4 / 127 |
Outcome results
Primary
Rate of Paclitaxel Treatment Completion Within 7 Weeks
Rate of participants who completed Paclitaxel treatment in 7 weeks while omitting Neulasta™ (Pegfilgrastim). Neulasta is administered based on the following pre-specified safety criteria. * The patient experiences a prior episode of fever and neutropenia. * If the patient has an active infection this decision will be at provider discretion.
Time frame: 7 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Rate of Paclitaxel Treatment Completion Within 7 Weeks | 90 percentage of participants |
Secondary
Median of Savings When Omitting Pegfilgrastim From Treatment.
An algorithm was used to estimated median and range of potential savings per 100 patients if the use of pegfilgrastim was omitted from treatment. The algorithm is designed assuming an average wholesale price in the United States ranging from $1,361 to $4,655 for myeloid growth factors such as filgrastim (8 days of growth factor support/cycle) and peg-filgrastim ($5,443 to $18,622 for 4 cycles on the basis of April 2019 Medicare Part B Drug Average Sales Price), and applying a 95.7% reduction in the use of pegfilgrastim during paclitaxel.
Time frame: While on treatment, up to 2.3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel | Median of Savings When Omitting Pegfilgrastim From Treatment. | 1.1 millions of dollars per 100 patients |
Secondary
Number of Participants With Dose Delays by Reason for Delay
Number of participants with dose delays due to various different adverse events. Adverse events classified using CTCAEv 4.0.
Time frame: While on treatment, up to 2.3 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Cardiotoxicity | 1 Participants |
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Febrile Neutropenia | 1 Participants |
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Neutropenia without Fever | 12 Participants |
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Nonhematologic Toxicity | 3 Participants |
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Infection | 1 Participants |
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Neurotoxicity | 3 Participants |
| Paclitaxel | Number of Participants With Dose Delays by Reason for Delay | Other | 3 Participants |
Secondary
Percentage of Participants Who Received All Planned Chemotherapy Cycles
Percentage of Participants who received all planned chemotherapy cycles.
Time frame: While on treatment, up to 2.3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Percentage of Participants Who Received All Planned Chemotherapy Cycles | 92 percentage of participants |
Secondary
Rate of Chemotherapy Dose Reductions
Percentage of participants experiencing dose reductions due to adverse events.
Time frame: While on treatment, up to 2.3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Rate of Chemotherapy Dose Reductions | 13.6 percentage of participants |
Secondary
Rate of Grade 3-4 Toxicities, Excluding Neutropenia
Percentage of participants experiencing a grade 3 or 4 toxicity excluding grade 3 or 4 neutropenia or febrile neutropenia per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: While on study, up to 6.2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Rate of Grade 3-4 Toxicities, Excluding Neutropenia | 12 percentage of participants |
Secondary
Rate of Grade 3-5 Neutropenia
Percentage of participants experiencing grade 3-5 neutropenia per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. while on treatment.
Time frame: While on study, up to 6.2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Rate of Grade 3-5 Neutropenia | 8.8 percentage of participants |
Secondary
Rate of Hypersensitivity Reactions on Cycles 3-4 of Paclitaxel, When Steroid is Avoided
The percentage of participants who experienced a hypersensitivity reaction on cycles 3 and 4 without use of dexamethasone (a steroid)..
Time frame: While on treatment, up to 2.3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel | Rate of Hypersensitivity Reactions on Cycles 3-4 of Paclitaxel, When Steroid is Avoided | 2.4 percentage of participants |