Neoadjuvant Chemotherapy Using Doxorubicin and Paclitaxel in Treating Women With Large Breast Cancer
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 120 |
| Updated: | 4/21/2016 |
| Start Date: | February 2000 |
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.
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.
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.
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.
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
We found this trial at
2
sites
Massachusetts General Hospital Cancer Center An integral part of one of the world
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