Dose Dense TC + Pegfilgrastim Support for Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the feasibility of giving standard TC chemotherapy on a dose dense schedule (ddTC) as well as evaluating the nature and frequency of ddTC side effects.

Detailed Description
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A standard chemotherapy treatment option for breast cancer after surgery (adjuvant therapy) is docetaxel + cyclophosphamide (TC). This study looks at a different schedule for giving the same adjuvant chemotherapy so that treatment can be completed faster (in 8 weeks rather than 12 weeks). This study uses a growth factor drug, pegfilgrastim, to help build blood cells that are lowered because of chemotherapy, making it possible to receive TC treatment every 2 weeks (referred to as dose dense TC or ddTC) instead of the standard 3 week schedule. The main study procedures are blood draws, chemotherapy treatment, physical exams, and pegfilgrastim injections.

Official Title
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Phase II Study of Dose-Dense TC (Docetaxel + Cyclophosphamide) With Pegfilgrastim Support for Adjuvant Therapy of pN0, pN1 or Nx Breast Cancer

Conditions
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Female Breast Cancer

Intervention / Treatment
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* Drug: docetaxel + cyclophosphamide + pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed invasive carcinoma of the female breast, status post definitive surgery (lumpectomy or mastectomy plus nodal evaluation if feasible). Patients must initiate therapy with ddTC within 84 days of the last breast or axillary surgery performed for curative intent candidate for chemotherapy by the treating oncologist Patients with pN2 or pN3 disease are NOT explicitly excluded. However, patients with N2 or N3 disease MUST be reviewed with the PI or study chair before being enrolled on the study as TC would not normally be considered adequate therapy for such patients. Patients with bilateral, synchronous invasive breast cancer are eligible as long as both primary tumors meet the eligibility criteria. Patients with estrogen-receptor (ER) and/or progesterone receptor (PR) negative, positive, or unknown tumors are eligible. Patients with HER2 positive, negative or unknown disease are eligible for this trial. Patients whose tumors are HER2 positive by either immunohistochemistry (IHC) 3+ staining or demonstrate gene amplification by FISH should receive trastuzumab, following completion of adjuvant cytotoxic therapy with 4 cycles of ddTC. There must be negative surgical margins for invasive cancer and DCIS. LCIS is acceptable at the margin. Patients with multi-centric breast cancer are eligible as long as all known disease is resected from the breast with negative margins. Age >18 years. ECOG performance status ≤ 1 Women of childbearing potential should have a negative urine or blood beta-HCG, and must agree to contraception if engaging in sexual activity. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Women must not be pregnant or nursing as the chemotherapy drugs used in this study may cause harm to a fetus or newborn. Ability to understand and the willingness to sign a written informed consent document. Platelets >/=100,000/μl within 4 weeks of registration. Absolute neutrophil count (ANC) >/= 1,500/μl within 4 weeks of registration. Total bilirubin within normal institutional limits within 4 weeks of registration. Alkaline phosphatase (alk phos) ≤ 2.5 X institutional Upper Limit of Normal (ULN) within 4 weeks of registration. AST (SGOT)/ALT(SGPT) ≤ 1.5X ULN Creatinine within normal institutional limits OR Creatinine clearance>/= 60 mL/min/1.73 m2 for patients with creatinine levels above normal If patient has received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indications (not for treatment of this cancer), they have been discontinued prior to enrollment. Exclusion Criteria: Patient has received previous trastuzumab, chemotherapy, hormonal therapy, or other anti-cancer agents (including investigational agents) for this malignancy. Patient will be receiving GNRH agonists such as goserelin (Zoladex) or leuprolide acetate (Lupron) concomitantly with chemotherapy for the purpose of preventing breast cancer recurrence. Patient has inflammatory breast cancer (pT4d) or metastatic breast cancer. Patient has uncontrolled intercurrent illness including, but 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. Patient has pre-existing persistent neuropathy. The patient has received prior chemotherapy or radiotherapy or any malignancy within the past 2 years. Patient has received prior docetaxel or cyclophosphamide within the past 5 years. Patient has known contraindication or hypersensitivity to docetaxel, cyclophosphamide or pegfilgrastim.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose dense TC + pegfilgrastim<br>Docetaxel + Cyclophosphamide chemotherapy given every 2 weeks x 4 cycles plus pegfilgrastim given 24-48 hours post day 1 of each cycle | Drug: docetaxel + cyclophosphamide + pegfilgrastim<br>* docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 IV every 2 weeks x 4 cycles plus pegfilgrastim 6mg sq 24-48 hours post day 1 of each cycle<br>* Other names: Taxotere, Cytoxan, Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility for Dose-dense TC Therapy: Number of Participants Receiving at Least 90% of Total Dose of Therapy | Evaluate feasibility of delivering 4 cycles (1 cycle = 2 weeks) of docetaxel and cyclophosphamide (TC) on a dose-dense (q2week) schedule with pegfilgrastim support. This regimen will be referred to as dose-dense (dd)TC. Feasibility defined by at least 60% of patients receiving 90% of the total dose of therapy within 10 weeks. | 4 cycles each 2 weeks in length for a total of 8 weeks, up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Febrile Neutropenia | Neutropenic fever was anticipated to be a clinically significant toxicity that would limit the maximal density of TC therapy. | Up to 10 weeks | 
| Incidence of Neuropathy | Neuropathy was anticipated to be a clinically significant toxicity that would limit the maximal density of TC therapy. | Up to 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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female, women, adjuvant, breast cancer