Condition category
Cancer
Date applied
24/03/2010
Date assigned
14/04/2010
Last edited
14/04/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.cancer.gov/clinicaltrials/DFCI-99278

Contact information

Type

Scientific

Primary contact

Dr Alphonse Taghian

ORCID ID

Contact details

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

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

http://www.cancer.gov/researchandfunding/

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

  1. 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.

  2. 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.

Additional files

Editorial Notes