HER2-positive Breast Cancer
Conditions
Brief summary
This study is to see how safe the use of short-term fasting is in breast cancer patients who will receive chemotherapy before undergoing surgery and to examine if the use of short-term fasting will decrease the side effects of chemotherapy and how much a tumor shrinks while receiving chemotherapy.
Detailed description
Patients will fast 24 hours before and 24 hours after the administration of chemotherapy which will consist of doxorubicin plus cyclophosphamide every 2 weeks for four cycles followed by paclitaxel every 2 weeks for four cycles (dose-dense AC + T) or docetaxel (T) every 3 weeks for four cycles. Trastuzumab (H) and Pertuzumab (P) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pathological complete remission (pCR), adjuvant chemotherapy with doxorubicin (A) plus cyclophosphamide (C) every 3 weeks for four cycles will be given, followed by trastuzumab every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).
Interventions
DRUGDoxorubicin
doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 2 weeks for four cycles followed by paclitaxel (T) 75 mg/m2 every 2 weeks for four cycles (dose-dense AC + T).20
DRUGcyclophosphamide
doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 2 weeks for four cycles followed by paclitaxel (T) 75 mg/m2 every 2 weeks for four cycles (dose-dense AC + T).20
DRUGpaclitaxel
For patients with HER2 negative breast cancer: doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 2 weeks for four cycles followed by paclitaxel (T) 75 mg/m2 every 2 weeks for four cycles (dose-dense AC + T).20
DRUGdocetaxel
For patients with HER2 positive breast cancer: docetaxel (T) 75 mg/m2 every 3 weeks for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent 3 cycles), Pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pCR, adjuvant chemotherapy with doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles will be given, followed by trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab 6 mg/kg every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).21
DRUGTrastuzumab
docetaxel (T) 75 mg/m2 every 3 weeks for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent 3 cycles), Pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pCR, adjuvant chemotherapy with doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles will be given, followed by trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab 6 mg/kg every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).21
DRUGPertuzumab
docetaxel (T) 75 mg/m2 every 3 weeks for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent 3 cycles), Pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. For patients who do not achieve pCR, adjuvant chemotherapy with doxorubicin (A) 60 mg/m2 plus cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles will be given, followed by trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment. For patients with pCR, only trastuzumab 6 mg/kg every 3 weeks will be given adjuvantly to complete 1 year of treatment (TPH + AC).21
Sponsors
Western Regional Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years of age with histologically, and radiographically confirmed non-metastatic breast cancer with minimal tumor size over 1 cm (≥T1c lesion) to receive neoadjuvant chemotherapy recommended by the treating physician * For estrogen receptor (ER) strongly positive, human epithelial receptor (HER2) negative breast cancer, Oncotype Dx study is required. Patients with low recurrence score will be excluded in the study. * Eastern Cooperative Oncology Group (ECOG) performance status score \< 1 * Absolute neutrophil count \> 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5 g/dL * Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 1.5 X ULN (≤ 3 mg/dL if clinically diagnosed with Gilbert syndrome) AST/ALT ≤ 2.5 X ULN (AST/ALT ≤ 5X ULN if clinically diagnosed with Gilbert syndrome) * Willing to provide blood samples for correlative research purposes * Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.
Exclusion criteria
1. Uncontrolled cardiac disease, such as angina, hypertension or significant arrhythmias, congestive heart failure (NYHA grade 2 or more or LVEF \< 40% on any prior assessment). Note: Assessment of LVEF is done before and after anthracycline-based or trastuzumab-based chemotherapy as standard of care 2. Pregnant or lactating females 3. Known history of diabetes mellitus. If screening fasting glucose is ≥126 mg/dL, an HbA1C must be \< 6.5%. 4. History of syncope with calorie restriction in the past 5. Body mass index (BMI) \< 19 kg/m2 6. Clinical signs or symptoms of GI obstruction and/or requirement for parenteral hydration or nutrition 7. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements 8. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements 9. Any other medical comorbidity that requires daily medication(s) that may not be safely taken without food.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Response Rate at the Time of Surgery or at the Time of Biopsy | 4-6 cycles (up to 12 weeks) | Evaluate pathological complete remission rate at the time of surgery, or partial pathological response rate (defined as residual invasive disease of 1cm) at the time of surgery or at the time of biopsy upon completion of planned chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Response Rate at the Time of Surgery or Time of Biopsy Upon Completion of Planned Chemotherapy | 4-6 cycles | To evaluate pathological complete remission rate (defined as disappearance of all invasive tumor in the breast; ypT0-is) at the time of surgery, or partial pathological response rate (defined as residual invasive disease of 1cm, ypT1a-b) at the time of surgery or at the time of biopsy upon completion of planned chemotherapy for triple-negative breast cancer. |
| Insulin Abnormalities | 4-6 cycles (up to 12 weeks) | Changes in plasma insulin abnormalities after short-term fasting and chemotherapy |
| Biomarker Changes Before and After Chemotherapy | 4-6 cycles (up to 12 weeks) | Biomarker changes in breast cancer (biopsy or residual tumor) before and after neoadjuvant chemotherapy |
| Fasting on the Toxicity of Neoadjuvant Chemotherapyaccording to the NCI | 4-6 cycles (up to 12 weeks) | The effect of short-term fasting on the toxicity of neoadjuvant chemotherapy in breast cancer patients according to the NCI common toxicity criteria (Version 4.03) |
| Glucose After Fasting and Chemotherapy | 4-6 cycles (up to 12 weeks) | To investigate changes in glucose after short-term fasting and chemotherapy |
| Changes in Insulin-like Growth Factor-1 | 4-6 cycles (up to 12 weeks) | To investigate changes in Insulin-like growth factor-1 (IGF1) after short-term fasting and chemotherapy |
| Plasma Blood-based Tumor-related Abnormalities in DNA | 4-6 cycles (up to 12 weeks) | To investigate changes in plasma blood-based tumor-related abnormalities in DNA after short-term fasting and chemotherapy |
| Nutritional Assessment Before and After Neoadjuvant Chemotherapy | 4-6 cycles (up to 12 weeks) | Nutritional status assessment with Patient Generated Subjective Global Assessment (aPG-SGA) before and after neoadjuvant chemotherapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnosed With HER2 Negative Breast Cancer Patients will receive doxorubicin and cyclophosphamide every two weeks for four cycles (one cycle is defined as 14 days). After completing fourth cycle, they will receive paclitaxel every two weeks for an additional four cycles. The appropriate surgery will be done three to six weeks after completing the last cycle of paclitaxel. | 0 |
| Diagnosed With HER2 Positive Breast Cancer will receive docetaxel, trastuzumab, and pertuzumab every three weeks for four cycles (one cycle is defined as 21 days). An injection of pegfilgrastim will be administered after chemotherapy with docetaxel. The appropriate surgery will be done three to six weeks after completing the last cycle of docatexel. If the study doctor determines that additional chemotherapy is needed (based on tumor shrinkage), patients will receive both doxorubicin and cyclophosphamide every three weeks for four cycles and after the fourth cycle you will receive trastuzumab every three weeks for one year or patients will receive trastuzumab alone every three weeks for up to one year | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Pathological Response Rate at the Time of Surgery or at the Time of Biopsy
Evaluate pathological complete remission rate at the time of surgery, or partial pathological response rate (defined as residual invasive disease of 1cm) at the time of surgery or at the time of biopsy upon completion of planned chemotherapy.
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information. After much effort, results were not able to be retained.
Secondary
Biomarker Changes Before and After Chemotherapy
Biomarker changes in breast cancer (biopsy or residual tumor) before and after neoadjuvant chemotherapy
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Changes in Insulin-like Growth Factor-1
To investigate changes in Insulin-like growth factor-1 (IGF1) after short-term fasting and chemotherapy
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Fasting on the Toxicity of Neoadjuvant Chemotherapyaccording to the NCI
The effect of short-term fasting on the toxicity of neoadjuvant chemotherapy in breast cancer patients according to the NCI common toxicity criteria (Version 4.03)
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Glucose After Fasting and Chemotherapy
To investigate changes in glucose after short-term fasting and chemotherapy
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Insulin Abnormalities
Changes in plasma insulin abnormalities after short-term fasting and chemotherapy
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Nutritional Assessment Before and After Neoadjuvant Chemotherapy
Nutritional status assessment with Patient Generated Subjective Global Assessment (aPG-SGA) before and after neoadjuvant chemotherapy
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Pathological Response Rate at the Time of Surgery or Time of Biopsy Upon Completion of Planned Chemotherapy
To evaluate pathological complete remission rate (defined as disappearance of all invasive tumor in the breast; ypT0-is) at the time of surgery, or partial pathological response rate (defined as residual invasive disease of 1cm, ypT1a-b) at the time of surgery or at the time of biopsy upon completion of planned chemotherapy for triple-negative breast cancer.
Time frame: 4-6 cycles
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.
Secondary
Plasma Blood-based Tumor-related Abnormalities in DNA
To investigate changes in plasma blood-based tumor-related abnormalities in DNA after short-term fasting and chemotherapy
Time frame: 4-6 cycles (up to 12 weeks)
Population: Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information.After much effort, results were not able to be retained.