Cyclophosphamide and Paclitaxel With or Without Trastuzumab in Stage I-II Breast Cancer Who Have Undergone Surgery

Phase 2

Completed

• Conditions: Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer
• Interventions: Drug: cyclophosphamide; Drug: paclitaxel; Biological: trastuzumab; Other: laboratory biomarker analysis

• Registration Number: NCT01106898
• Lead Sponsor: University of Nebraska

Brief Summary

This phase II trial studies the side effects and how well giving cyclophosphamide and paclitaxel with or without trastuzumab works in treating patients with stage I-II breast cancer who have undergone surgery. Drugs used in chemotherapy, such as cyclophosphamide and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy, such as trastuzumab, with chemotherapy may kill more tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the toxicities and ability to complete the planned treatment of a dose-dense regimen of cyclophosphamide and paclitaxel with or without trastuzumab in patients with newly diagnosed stage I-II breast cancer.

II. To estimate recurrence free survival of a dose-dense regimen of cyclophosphamide and paclitaxel with or without trastuzumab in patients with newly diagnosed stage I-II breast cancer.

OUTLINE:

SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY (human epidermal growth factor receptor 2 \[Her-2\] neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 3 years.

Study Timeline

• Study Start: 2010-03-24
• Study First Submitted: 2010-04-13
• Study First Submitted QC: 2010-04-16
• Study First Posted: 2010-04-20
• Primary Completion: 2015-09-28
• Study Completion: 2015-09-28
• Results First Submitted: 2018-04-30
• Results First Submitted QC: 2018-04-30
• Results First Posted: 2018-05-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-13
• Last Update Posted: 2023-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 112

Inclusion Criteria

• Histologically confirmed newly diagnosed stage I-II breast cancer
• Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
• Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count greater than or equal to 1,500/mcl
• Platelet count equal to or greater than 150,000/mcl
• Hemoglobin > 11 gm/dl
• Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN)
• Total bilirubin equal to or less than 1.5 times the ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times the ULN
• Creatinine less than 1.5 times the ULN
• Able to give informed consent
• All included patients must have normal cardiac function as defined by an ejection fraction of > 50% by echocardiogram
• Able to return for treatment and follow-up on the specified days

Exclusion Criteria

• Prior malignancy; except for adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas
• Patients with preexisting grade II peripheral neuropathy
• Patients with prior chemotherapy
• Stage IV or metastatic breast cancer
• Pregnant or nursing women
• Inability to cooperate with treatment protocol
• No active serious infections or other conditions precluding chemotherapy
• Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol (e.g. unstable angina, myocardial infarction within 6 months, severe infection, etc.)
• Known hypersensitivity to any component of required drugs in the study
• Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C or active hepatitis
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiograph (ECG) abnormality at screening has to be documented by the investigator as not medically relevant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy with or without maintenance therapy)	trastuzumab	SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (Her-2 neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity.
Treatment (chemotherapy with or without maintenance therapy)	laboratory biomarker analysis	SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (Her-2 neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity.
Treatment (chemotherapy with or without maintenance therapy)	cyclophosphamide	SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (Her-2 neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity.
Treatment (chemotherapy with or without maintenance therapy)	paclitaxel	SYSTEMIC CHEMOTHERAPY: Patients receive cyclophosphamide IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (Her-2 neu positive patients): Patients receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 5 courses and then every 21 days for 14 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Recurrence-free Survival	Time from the start of treatment to recurrence, second malignancy, or death as a first event, assessed up to 3 years	Recurrence-free survival curves will be plotted for subjects treated with stage I and II disease.

Trial Locations

Locations (2)

Saint Francis Medical Center; 🇺🇸 Grand Island, Nebraska, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States