Plain English Summary
Not provided at time of registration
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00096291
Protocol/serial number
CDR0000382123, DFCI-99278
Study information
Scientific title
A Multicentre, Phase II, Neoadjuvant Chemotherapy in Palpable Breast Cancer: Evaluation of Physiologic, Radiologic, and Molecular Markers in Predicting Response
Acronym
Study hypothesis
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.
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
Massachusetts General Hospital - Dana-Farber Cancer Institute (MGH-DFCI) Institutional Review Board (IRB) approved on the 15th of May 2000 (ref: 1999P010935)
Study design
Multicentre phase II randomized active controlled parallel group comparative trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Patient information can be found at http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=382123&version=patient
Condition
Breast cancer
Intervention
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, 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 type
Other
Phase
Phase II
Drug names
Primary outcome measures
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.
Secondary outcome measures
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.
Overall trial start date
01/06/2000
Overall trial end date
30/05/2004
Reason abandoned
Eligibility
Participant inclusion criteria
1. 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%
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Total of 100 patients (50 per treatment arm) accrued within 4-5 years
Participant exclusion criteria
1. 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
Recruitment start date
01/06/2000
Recruitment end date
30/05/2004
Locations
Countries of recruitment
United States of America
Trial participating centre
Department of Radiation Oncology, Massachusetts General Hospital
Boston
02114
United States of America
Sponsor information
Organisation
National Cancer Institute (NCI) (USA)
Sponsor details
NCI Public Inquiries Office
6116 Executive Boulevard
Room 3036A
Bethesda
20892-8322
United States of America
+1 800 422 6237
weissl@nih.gov
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
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)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2005 results in http://www.ncbi.nlm.nih.gov/pubmed/15774788
2. 2005 results on comparison of mammography, sonography, and MRI in http://www.ncbi.nlm.nih.gov/pubmed/15728611
Publication citations
-
Taghian AG, Abi-Raad R, Assaad SI, Casty A, Ancukiewicz M, Yeh E, Molokhia P, Attia K, Sullivan T, Kuter I, Boucher Y, Powell SN, Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications., J. Clin. Oncol., 2005, 23, 9, 1951-1961, doi: 10.1200/JCO.2005.08.119.
-
Yeh E, Slanetz P, Kopans DB, Rafferty E, Georgian-Smith D, Moy L, Halpern E, Moore R, Kuter I, Taghian A, Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer., AJR Am J Roentgenol, 2005, 184, 3, 868-877, doi: 10.2214/ajr.184.3.01840868.