Clinical trial · Interventional

Combination Chemotherapy, Surgery, and Radiation Therapy With or Without Dexrazoxane and Trastuzumab in Treating Women With Stage III or Stage IV Breast Cancer

A 2X2X2 Factorial Randomized Phase III Trial Of Multimodality Therapy Comparing 4 Cycles Of Doxorubicin And Cyclophosphamide With Or Without Dexrazoxane (AC+/-Z) Followed By 12 Weeks Of Weekly Paclitaxel With Or Without Trastuzumab (T+/-H) Followed By Local Therapy Followed By 40 Weeks Of Weekly Trastuzumab Or None In Women With HER-2+ STAGE IIIA, IIIB OR REGIONAL STAGE IV BREAST CANCER

NCT00016276CI-TRIAL-00008956terminatedPhase 3ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): Administratively complete.

Summary

Brief summary (as posted)

Randomized phase III trial to compare the effectiveness of combination chemotherapy, surgery, and radiation therapy with or without dexrazoxane and trastuzumab in treating women who have stage IIIA, stage IIIB or stage IV breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as dexrazoxane, may protect normal cells from the side effects of chemotherapy. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy combined with surgery and radiation therapy is more effective with or without dexrazoxane and trastuzumab in treating breast cancer

Conditions

Conditions (5)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Cardiac Toxicity	—	UNRESOLVED	—
Inflammatory Breast Cancer	Breast Inflammatory Carcinoma	ALIAS	0.90
Stage IIIA Breast Cancer	Malignant Breast Neoplasm	CURATED_BROADER	0.78
Stage IIIB Breast Cancer	Malignant Breast Neoplasm	CURATED_BROADER	0.78
Stage IV Breast Cancer	Malignant Breast Neoplasm	CURATED_BROADER	0.78

Interventions

Interventions (9)

Intervention	Type	Mapped drug	Match
cyclophosphamide	Drug	Cyclophosphamide	ALIAS
dexrazoxane hydrochloride	Drug	—	UNRESOLVED
doxorubicin hydrochloride	Drug	Doxorubicin	ALIAS
laboratory biomarker analysis	Other	—	UNRESOLVED
paclitaxel	Drug	Paclitaxel	ALIAS
radiation therapy	Radiation	—	UNRESOLVED
tamoxifen citrate	Drug	Tamoxifen	ALIAS
therapeutic conventional surgery	Procedure	—	UNRESOLVED

Design

Arms and outcomes

Arms (8)

type
EXPERIMENTAL
label
Arm I (chemoprotection, monoclonal antibody, radiotherapy)
description
Patients receive dexrazoxane IV over 10-20 minutes, doxorubicin IV over 5-10 minutes, and cyclophosphamide IV over 30 minutes on days 1, 22, 43, and 64. Patients receive paclitaxel IV over 1 hour and trastuzumab (Herceptin) IV over 30-90 minutes on days 85, 92, 99, 106, 113, 120, 127, 134, 141, 148, 155, and 162. Approximately 1-2 weeks after completion of neoadjuvant chemotherapy, patients undergo breast conservation surgery, modified radical mastectomy, or mastectomy. Patients with unacceptable toxicity or locoregional disease progression may undergo surgery prior to week 24 (i.e., completion of neoadjuvant chemotherapy). Beginning 2-4 weeks after breast conservation surgery or 3-5 weeks after mastectomy, patients undergo radiotherapy daily 5 days a week for 6-8 weeks. Patients receive long-term trastuzumab IV over 30-90 minutes weekly for 40 weeks beginning on week 36 (day 254).
interventionNames
1. Drug: dexrazoxane hydrochloride
2. Drug: doxorubicin hydrochloride
3. Drug: cyclophosphamide
4. Drug: paclitaxel
5. Biological: trastuzumab
6. Procedure: therapeutic conventional surgery
7. Radiation: radiation therapy
8. Drug: tamoxifen citrate
9. Other: laboratory biomarker analysis
type

Eligibility

Eligibility (as posted)

Sex: Female
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

* Histologically confirmed primary infiltrating adenocarcinoma of the breast

  * Confirmed by core needle biopsy or incisional biopsy
  * Amplification of HER-2 by FISH
  * Overexpression (3+) of HER-2 by immunohistochemistry
  * Staging criteria after complete clinical and radiographic staging:

    * T3, N1, M0
    * Any T, N2 or N3, M0
    * T4, any N, M0, including clinical or pathological inflammatory disease
    * Regional stage IV disease with supraclavicular or infraclavicular lymph nodes as only site of metastasis
* Measurable or evaluable disease
* Prior ductal carcinoma in situ of the ipsilateral breast allowed if treated with excision only without mastectomy or radiation
* Metaplastic carcinoma allowed
* Synchronous bilateral primary disease allowed (provided at least 1 cancer meets staging criteria)
* No dermal lymphatic involvement with clinical inflammatory changes
* Hormone receptor status:

  * Estrogen receptor positive or negative
  * Progesterone receptor positive or negative
* Female
* Granulocyte count at least 1,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than upper limit of normal (ULN)
* AST no greater than 2 times ULN
* Creatinine no greater than 1.5 times ULN
* LVEF normal by MUGA
* No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction within the past 6 months, congestive heart failure treated with medications, or uncontrolled hypertension)
* No other currently active malignancy except nonmelanoma skin cancer
* Not pregnant or nursing
* Fertile patients must use effective contraception
* Patients taking tamoxifen must use effective nonhormonal contraception during and for 2 months after study
* No prior chemotherapy
* No other concurrent chemotherapy
* No more than 4 weeks of prior tamoxifen for disease
* Prior tamoxifen or raloxifene for longer than 4 weeks as chemoprevention allowed
* No concurrent tamoxifen or raloxifene
* No other concurrent hormonal therapy except for steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic
* See Disease Characteristics
* No prior radiotherapy for index malignancy
* No prior radiotherapy to the ipsilateral breast, regional nodes, mediastinum, or heart
* Prior radiotherapy to the contralateral breast for ductal carcinoma in situ or early stage invasive breast cancer allowed provided earlier radiotherapy does not preclude optimal delivery of study radiotherapy and criterion of low risk for metastasis from first malignancy is met
* See Disease Characteristics
* No prior sentinel lymph node biopsy

References

Publications (0)

Data not yet available

No reference posted for this study.

Registry

Dates and enrollment

Start: May 1, 2001
Primary completion: Mar 1, 2005
Completion: —
First posted: Sep 4, 2003
Last update posted: Jan 16, 2013
Enrollment: 396 (actual)
Lead sponsor: National Cancer Institute (NCI) NIH

Data updated 22 days agoSource updated Jan 16, 2013source: clinicaltrials

Locations

Locations by country (1)

Country	Sites	Recruiting
United States	1	0

Trial listing is informational. Eligibility is decided by the study team; contact information is on ClinicalTrials.gov.