Clinical trial NCT00801411: Cyclophosphamide and Docetaxel or Doxorubicin in Treating Women With Newly Diagnosed Breast Cancer That Can Be Removed by Surgery
Official title: A Randomised Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide Compared to Doxorubicin and Cyclophosphamide in Operable Node Negative Breast Cancer With Normal Topoisomerase IIα Expression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage II breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-12-03
Enrollment: 318
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, docetaxel, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which chemotherapy regimen is more effective in treating breast cancer.

PURPOSE: This randomized phase II trial is studying cyclophosphamide given together with docetaxel to see how well it works compared with cyclophosphamide given together with doxorubicin in treating women with newly diagnosed breast cancer that can be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To evaluate tumor pathological complete response rate after neoadjuvant cyclophosphamide in combination with docetaxel vs doxorubicin hydrochloride in women with operable clinically node-negative breast cancer and normal topoisomerase IIα expression.

Secondary

* To assess tumor clinical and pathological overall response rates in patients treated with these regimens.
* To assess the safety and toxicity of these regimens.
* To assess disease-free survival and overall survival of these patients.
* To assess the efficacy of short-course (3 days) filgrastim (G-CSF) as primary and secondary prophylaxis against febrile neutropenia in patients receiving docetaxel and cyclophosphamide.

OUTLINE: This is a multicenter study.

Patients are stratified according to hormone receptor status (estrogen receptor \[ER\]- or progesterone receptor \[PR\]-positive vs ER- and PR-negative) and T stage (T2 vs T3). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive cyclophosphamide IV and docetaxel IV over 1 hour on day 1.
* Arm II: Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1.

In both arms, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of neoadjuvant chemotherapy, all patients undergo surgery.

Tumor specimens obtained prior to neoadjuvant chemotherapy are analyzed for topoisomerase IIα gene and protein expression by IHC and FISH. Tissue samples are also collected at surgery for future studies.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed invasive breast cancer

  * Newly diagnosed disease
  * Operable disease
* Must have clinical T2 (\> 2cm) or T3 (\> 5 cm) primary tumors with no clinical lymph node involvement (N0)

  * No clinical T4 lesion (e.g., peau d'orange, skin ulceration, satellite nodules, or inflammatory breast cancer)
* No evidence of metastatic disease
* Known hormone receptor status

PATIENT CHARACTERISTICS:

* Menopausal status not specified
* ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
* Life expectancy \> 10 years
* Leukocytes ≥ 3,000/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Total bilirubin normal
* AST and ALT ≤ 2.5 times upper limit of normal
* Creatinine normal or creatinine clearance ≥ 40 mL/min
* Normal cardiac ejection fraction, defined as ≥ 50% by MUGA scan or 2D-ECHO
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or other agents used in this study
* No history of pre-existing peripheral neuropathy
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
* No prior malignancies except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy or radiotherapy
* No other concurrent investigational or commercial agents or therapies with the intent to treat the patient's malignancy
* No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, surgery for cancer, or experimental medications
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent antitumor therapy

Primary outcomes:
measure: Pathological complete response rate
Secondary outcomes:
measure: Clinical and pathological overall response rate
measure: Toxicity as assessed by NCI CTCAE v3.0
measure: Overall survival
measure: Disease-free survival
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre - Singapore
Study officials:
affiliation: National Cancer Centre, Singapore
name: Wong Nan Soon, MBBS, MRCP, FAMS
role: PRINCIPAL_INVESTIGATOR
References: