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 number | NCT00096291 |
| Secondary identifying numbers | CDR0000382123, DFCI-99278 |
- 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
Scientific
Department of Radiation Oncology, Massachusetts General Hospital
100 Blossom Street
Cox Building 302
Boston
02114
United States of America
Study information
| Study design | Multicentre phase II randomized active controlled parallel group comparative trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Patient information can be found at http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=382123&version=patient |
| Scientific title | A Multicentre, Phase II, Neoadjuvant Chemotherapy in Palpable Breast Cancer: Evaluation of Physiologic, Radiologic, and Molecular Markers in Predicting Response |
| Study objectives | 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(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) studied | 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 |
| Primary outcome measure | 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 study start date | 01/06/2000 |
| Completion date | 30/05/2004 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Total of 100 patients (50 per treatment arm) accrued within 4-5 years |
| Key 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% |
| Key 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 |
| Date of first enrolment | 01/06/2000 |
| Date of final enrolment | 30/05/2004 |
Locations
Countries of recruitment
- United States of America
Study participating centre
Department of Radiation Oncology, Massachusetts General Hospital
Boston
02114
United States of America
02114
United States of America
Sponsor information
National Cancer Institute (NCI) (USA)
Research organisation
Research organisation
NCI Public Inquiries Office
6116 Executive Boulevard
Room 3036A
Bethesda
20892-8322
United States of America
| Phone | +1 800 422 6237 |
|---|---|
| weissl@nih.gov | |
| Website | http://www.cancer.gov/researchandfunding/ |
"ROR" |
https://ror.org/040gcmg81 |
Funders
Funder type
Research organisation
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)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not 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 |
