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Neoadjuvant Chemotherapy Using Doxorubicin and Paclitaxel in Treating Women With Large Breast Cancer

7 апреля 2017 г. обновлено: Alphonse Taghian, MD, PhD, Massachusetts General Hospital

Neoadjuvant Chemotherapy in Palpable Breast Cancer: Evaluation of Physiologic, Radiologic, and Molecular Markers in Predicting Response

RATIONALE: Drugs used in chemotherapy, such as doxorubicin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.

PURPOSE: This randomized phase II trial is comparing two different regimens of doxorubicin and paclitaxel to see how well they work in treating women who are undergoing surgery for breast cancer.

Обзор исследования

Статус

Завершенный

Условия

Рак молочной железы

Вмешательство/лечение

Подробное описание

OBJECTIVES:

Primary

Determine whether tumors in women with palpable invasive breast cancer with wild type p53 are more sensitive to doxorubicin than to paclitaxel when given as sequential single-agent neoadjuvant chemotherapy.
Determine whether tumors with inactivated p53 are more sensitive to paclitaxel than to doxorubicin when given as sequential single-agent neoadjuvant chemotherapy in these patients.

Secondary

Correlate other biological markers (physiological and molecular) with tumor response in patients treated with these regimens.
Determine changes in these biological markers during and after neoadjuvant chemotherapy in these patients.
Compare breast MRI, in terms of assessing tumor response, with physical exam, mammogram, and ultrasound in patients treated with these regimens.
Determine whether there are MRI indicators (e.g., tumor morphology or lesion enhancement) that are predictive of response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (> 5 cm vs ≤ 3-5 cm) and presence of palpable regional lymph nodes (yes vs no). Patients are randomized to 1 of 2 treatment arms.

All patients undergo biopsy, bilateral mammogram, MRI, ultrasound, blood marker, molecular (gene microarrays and functional p53 status), and physiologic studies before initiation of neoadjuvant chemotherapy. Some of these studies are repeated after completion of treatment with the first chemotherapeutic agent and after completion of treatment with the second chemotherapeutic agent as outlined below.

Arm I: Patients receive doxorubicin IV on days 1, 15, 29, and 43. Patients with no residual tumor (indicated by clinical evaluation and radiologic studies) after completion of doxorubicin undergo definitive surgery. After surgery, patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.

Patients with residual tumor > 2 cm after completion of doxorubicin undergo 8-12 core needle biopsies. Patients with residual tumor < 2 cm after completion of doxorubicin undergo 4-6 core needle biopsies. After core needle biopsies, patients receive paclitaxel as above.

Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients with no residual tumor (indicated by clinical evaluation and radiologic studies) after completion of paclitaxel undergo definitive surgery. After surgery, patients receive doxorubicin IV on days 1, 15, 29, and 43.

Patients with residual tumor > 2 cm after completion of paclitaxel undergo 8-12 core needle biopsies. Patients with residual tumor < 2 cm after completion of paclitaxel undergo 4-6 core needle biopsies. After core needle biopsies, patients receive doxorubicin as above.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Samples from core needle biopsies are analyzed by microarray analysis for gene expression profiles.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 4-5 years.

Тип исследования

Интервенционный

Регистрация (Действительный)

Фаза

Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

Соединенные Штаты
- Massachusetts
  - Boston, Massachusetts, Соединенные Штаты, 02115
    - Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  - Boston, Massachusetts, Соединенные Штаты, 02114-2617
    - Massachusetts General Hospital Cancer Center

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

От 18 лет до 120 лет (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Женский

Описание

DISEASE CHARACTERISTICS:

Diagnosis of invasive breast cancer
- Tumor ≥ 3 cm and palpable
  - Multiple masses are allowed provided at least 1 mass is ≥ 3 cm
- Clinically positive axillary or supraclavicular lymph nodes allowed
- Fine needle aspiration or core needle biopsy positive for invasive breast cancer AND/OR fine needle aspiration of lymph nodes positive
HER2/neu-positive OR negative
No inflammatory breast cancer
No distant metastases
Hormone receptor status:
- Estrogen receptor (ER)-positive OR ER-negative

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Female

Menopausal status

Premenopausal or postmenopausal

Performance status

Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

Granulocyte count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 2 times upper limit of normal (ULN)
SGOT ≤ 2 times ULN

Renal

Not specified

Cardiovascular

LVEF ≥ 50%
No congestive heart failure
No serious conduction system abnormality
No other significant cardiovascular disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Patients with other prior or concurrent malignancies allowed provided they have received no prior chemotherapy AND they are likely to have been cured from a prior malignancy
No severe medical or psychiatric condition that would preclude study compliance
No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy

Endocrine therapy

No prior hormonal therapy for breast cancer

Radiotherapy

No prior radiotherapy for this malignancy

Surgery

Not specified

Учебный план

В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

Основная цель: Фундаментальная наука
Распределение: Рандомизированный
Интервенционная модель: Параллельное назначение
Маскировка: Нет (открытая этикетка)

Количество рук

Оружие и интервенции

Группа участников / Армия	Вмешательство/лечение
Активный компаратор: Sequence Doxorubicin followed by Paclitaxel Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy: Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin	Другой: Doxorubicin followed by Paclitaxel Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy: Doxorubicin followed by Paclitaxel Paclitaxel followed by Doxorubicin Другой: Paclitaxel followed by Doxorubicin Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy: Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin
Другой: Sequence of neoadjuvant CT: Paclitaxel followed by Doxorubicin Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy: Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin	Другой: Paclitaxel followed by Doxorubicin Patients will be randomized into 2 groups based on sequence of neoadjuvant chemotherapy: Doxorubicin followed by Paclitaxel versus Paclitaxel followed by Doxorubicin