A Phase I Multi-Center Study to Evaluate the Safety, Tolerability, and Efficacy of Chemotherapeutic Regiments in Surgical Patients With Infiltrating Ductal Carcinoma of Breast
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 300
- Locations
- 3
- Primary Endpoint
- Incidence of treatment-emergent adverse events
Study Overview
Brief Summary
The overarching purpose of this study is to determine if the mainstay chemotherapeutic regimens represented by several genotoxic agents including but not limited to Cyclophosphamide, Doxorubicin, Epirubicin, Fluorouracil and Methotrexate (CDEFM), in the format of either a single agent or combinations are safe, tolerable, and effective in the treatment of patients with infiltrating ductal carcinoma of breast.
Detailed Description
Infiltrating ductal carcinoma (IDC) of breast, or sometimes called invasive ductal carcinoma of breast, is the most common type of breast malignancy. About 80% of all breast cancers are IDCs.
Once found, IDC usually has already broken through the wall of the milk duct and begun to invade the tissues of the breast. Over time, IDC can spread to the lymph nodes and possibly to other areas of the body with high frequency.
According to the statistics of American Cancer Society, more than 180,000 women in the United States are diagnosed with IDC each year. Although IDC can affect women at any age, it is more common as they grow older. Further, approximately two-thirds of women are 55 or older when they are diagnosed with such this symptom.
The treatments for invasive ductal carcinoma fall into two broad categories. First, local treatments for IDC, including surgery and radiation, which treat the primary tumor and surrounding areas such as the chest and lymph nodes. Second, systemic treatments for IDC, including chemotherapy, hormone therapy and targeted therapy, which are supposed to deliver cytotoxicity throughout the body to eliminate any cancer cells that have left the primary site and to help minimize the risk of recurrent disease.
PURPOSE: This randomized phase I trial is to determine the safety, tolerability and efficacy of single or concurrent administration of cyclophosphamide, doxorubicin, epirubicin, fluorouracil and methotrexate (CDEFM) to women undergoing surgery for infiltrating ductal carcinoma in situ breast cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients ≥ 18 years of age with histologically proven infiltrating ductal carcinoma of breast
- •no severe major organ dysfunction
- •Patients must have adequate hematopoietic function as evidenced by:
- •white blood cells (WBC) ≥ 3,000/μl absolute neutrophil count (ANC) ≥ 1,500/μl Platelet count ≥ 100,000/μl hemoglobin (HGB) ≥ 10 g/dl and not transfusion dependent
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10% above upper limit of normal
- •Individuals of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours of Cycle 1 Day
- •World Health Organization (WHO) performance status of 0 or 1
- •No prior or concurrent cancer-associated chemotherapy, no initiation of new hormonal therapy
- •Hormone receptor (estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 2 (Her2)) status not specified
- •Menopausal status not specified
- •Patients or their legal representatives must be willing and able to provide written informed consent
- •A Clinical Stage ≥ I subtype A (IA) (T1a, N0, M0) of Beast Cancer but without diagnosed distant metastasis (according to the 1997 revision of the International Union Against Cancer-PrimaryTumor, Regional Nodes and Metastasis (TNM) staging system) as determined by a preoperative evaluation that included a chest computed tomography (CT) scan and/or X-ray mammography.
Exclusion Criteria
- •Age < 18
- •Severe major organ dysfunction
- •WHO performance status of >1
- •Prior cancer chemotherapy
- •Patients with symptomatic central nervous system (CNS) metastases from breast cancer
- •Patients with a history of another invasive malignancy within the last 3 years
- •History of loss of consciousness or transient ischemic attack within 12 months before study treatment initiation.
- •Patients who have known active HIV, Hepatitis B, or Hepatitis C infections.
- •Patients with any other condition which in the opinion of the investigator would preclude participation in the study.
Arms & Interventions
Mono-chemotherapy
A mono-chemotherapy (a single chemotherapeutic agent out of cyclophosphamide, doxorubicin, epirubicin, fluorouracil and methotrexate (or CDEFM) was performed 30~60 days prior to surgery for patients who had no history of receiving either local or systemic cancer-associated chemotherapy.
Interventions: cyclophosphamide, doxorubicin, epirubicin, fluorouracil or methotrexate.
Intervention: Single agent of cyclophosphamide, doxorubicin, epirubicin, fluorouracil and methotrexate (Drug)
Combined chemotherapy
Combined chemotherapy (random combination of two breast cancer chemotherapeutic agents including cyclophosphamide, doxorubicin, epirubicin, fluorouracil and methotrexate, or CDEFM) was performed 30~60 days prior to surgery for patients who had no history of receiving either local or systemic chemotherapy for cancer.
Interventions: cyclophosphamide, doxorubicin, epirubicin, fluorouracil or methotrexate.
Intervention: cyclophosphamide, doxorubicin, epirubicin, fluorouracil and methotrexate (CDEFM) (Drug)
Placebo treatment
No chemotherapeutic regimes using any cytotoxic agent was done for patients who have infiltrating ductal carcinoma of breast. Placebo was used instead.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events
Time Frame: 6 months
The case of emergent events caused by treatment is measured by counting the blood cell number and detecting liver and kidney functions. Total blood cell number, alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) \> 20% above upper limit of normal, is considered as not safe. Tolerability is measured by monitoring the first occurrence of grade 4 hematologic or grade 3-4 non hematologic toxicity as defined by the National Cancer Institute (NCI)-Common Toxicity Criteria (CTC) (NCI-CTC version 4; or CTCAE v4.0) and/or disruption of chemotherapy because of inacceptable toxicity. Chemotherapeutic efficacy is measured by the remaining tumor size after computed tomography (CT) scanning and comparing it with the original primary tumor size 2-3 weeks after last cycle of chemotherapy. The ratio of post-treatment tumor size to pre-treatment tumor size \< 50% is considered as effective. Otherwise not.
Secondary Outcomes
- Circulating concentrations of tumor microenvironment-specific soluble factors(6 months)
Investigators
Yu Sun
Professor
Shanghai Jiao Tong University School of Medicine