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

ISRCTN ISRCTN12618919
DOI https://doi.org/10.1186/ISRCTN12618919
ClinicalTrials.gov (NCT) NCT00096291
Protocol serial number CDR0000382123, DFCI-99278
Sponsor National Cancer Institute (NCI) (USA)
Funder National Cancer Institute (NCI) (USA) - Avon-NCI Progress for Patients Award on the Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Breast Cancer (ref: CA089393)
Submission date
24/03/2010
Registration date
14/04/2010
Last edited
14/04/2010
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Alphonse Taghian
Scientific

Department of Radiation Oncology, Massachusetts General Hospital
100 Blossom Street
Cox Building 302
Boston
02114
United States of America

Study information

Primary study designInterventional
Study designMulticentre phase II randomized active controlled parallel group comparative trial
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleA Multicentre, Phase II, Neoadjuvant Chemotherapy in Palpable Breast Cancer: Evaluation of Physiologic, Radiologic, and Molecular Markers in Predicting Response
Study objectivesThis 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.

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.
Ethics approval(s)Massachusetts General Hospital - Dana-Farber Cancer Institute (MGH-DFCI) Institutional Review Board (IRB) approved on the 15th of May 2000 (ref: 1999P010935)
Health condition(s) or problem(s) studiedBreast cancer
InterventionThis 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, magnetic resonance imaging (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.

1. Arm I: Patients receive doxorubicin intravenously (IV) on days 1, 15, 29, and 43.
1.1. 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.
1.2. Patients with residual tumor > 2 cm after completion of doxorubicin undergo 8-12 core needle biopsies.
1.3. 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.

2. Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.
2.1. 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.
2.2. Patients with residual tumor > 2 cm after completion of paclitaxel undergo 8-12 core needle biopsies.
2.3. 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.
Intervention typeOther
Primary outcome measure(s)

1. 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.
2. 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.

Key secondary outcome measure(s)

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

Completion date30/05/2004

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target sample size at registration100
Key inclusion criteria1. Women, aged ≥ 18
2. Diagnosis of invasive breast cancer
3. Tumor more than 3 cm and palpable
4. Multiple masses are allowed provided at least 1 mass is more than 3 cm
5. Clinically positive axillary or supraclavicular lymph nodes allowed
6. Fine needle aspiration or core needle biopsy positive for invasive breast cancer AND/OR fine needle aspiration of lymph nodes positive
7. Estrogen receptor (ER)-positive OR ER-negative
8. ER2/neu-positive OR negative
9. Premenopausal or postmenopausal
10. Performance status: Karnofsky 60-100%
11. Granulocyte count more than 1,000/mm^3
12. Platelet count more than 100,000/cmm
13. Bilirubin more than 2 times upper limit of normal (ULN)
14. Serum glutamic oxaloacetic transaminase (SGOT) more than 2 times ULN
15. Left Ventricular Ejection Fraction (LVEF) not less than 50%
Key exclusion criteria1. Inflammatory breast cancer
2. Distant metastases
3. Congestive heart failure or other significant cardiovascular disease
4. Pregnancy or nursing
5. Severe medical or psychiatric condition that would preclude study compliance
6. HIV positivity
7. Patients with other prior or concurrent malignancies if they have received prior chemotherapy or are not cured from the prior malignancy
Date of first enrolment01/06/2000
Date of final enrolment30/05/2004

Locations

Countries of recruitment

  • United States of America

Study participating centre

Department of Radiation Oncology, Massachusetts General Hospital
Boston
02114
United States of America

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results on comparison of mammography, sonography, and MRI 01/03/2005 Yes No
Results article results 20/03/2005 Yes No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
Study website Study website 11/11/2025 11/11/2025 No Yes
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