Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Southwest Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005970
First received: July 5, 2000
Last updated: January 14, 2013
Last verified: January 2013
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Purpose
This randomized phase III trial is studying combination chemotherapy and trastuzumab to see how well they work compared to combination chemotherapy alone in treating women with breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer
| Condition | Intervention | Phase |
|---|---|---|
|
Stage I Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer |
Drug: doxorubicin hydrochloride Drug: cyclophosphamide Drug: paclitaxel Biological: trastuzumab Drug: tamoxifen citrate Drug: aromatase inhibition therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Overexpressing Node Positive or High-Risk Node Negative Breast Cancer |
Resource links provided by NLM:
Genetics Home Reference related topics:
breast cancer
Drug Information available for:
Cyclophosphamide
Tamoxifen
Doxorubicin
Doxorubicin hydrochloride
Paclitaxel
Tamoxifen citrate
Trastuzumab
U.S. FDA Resources
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Duration of disease-free survival (DFS) [ Time Frame: Time from registration to first adverse event, assessed up to 15 years ] [ Designated as safety issue: No ]Will be estimated using the Kaplan-Meier method.
Secondary Outcome Measures:
- Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 15 years ] [ Designated as safety issue: No ]Will be estimated using the Kaplan-Meier method.
| Estimated Enrollment: | 3000 |
| Study Start Date: | May 2000 |
| Estimated Primary Completion Date: | January 2100 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive doxorubicin IV and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Drug: tamoxifen citrate
Given orally
Other Names:
Drug: aromatase inhibition therapy
Given orally
Other Name: inhibition therapy, aromatase
|
|
Experimental: Arm II
Patients receive doxorubicin, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab (Herceptin®) IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.
|
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Biological: trastuzumab
Given IV
Other Names:
Drug: tamoxifen citrate
Given orally
Other Names:
Drug: aromatase inhibition therapy
Given orally
Other Name: inhibition therapy, aromatase
|
|
Experimental: Arm III
Patients receive doxorubicin and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy. |
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Biological: trastuzumab
Given IV
Other Names:
Drug: tamoxifen citrate
Given orally
Other Names:
Drug: aromatase inhibition therapy
Given orally
Other Name: inhibition therapy, aromatase
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Histologically confirmed operable adenocarcinoma of the breast, meeting 1 of the following criteria:
Node-positive disease, meeting the following criteria:
- One or more positive lymph nodes (T1-3, pN1-2, M0)
- No cN2 disease
- pN2 disease allowed
- One positive lymph node by sentinel node biopsy or at least 6 axillary nodes must be examined on axillary node dissection with at least 1 positive lymph node
- Metaplastic carcinoma allowed
High-risk node-negative disease, meeting the following criteria:
Node-negative as determined by 1 of the following:
- Negative sentinel node biopsy
- No positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection
- Tumor must be greater than 2.0 cm if estrogen-receptor (ER)- and progesterone-receptor (PR)-positive disease is present OR greater than 1.0 cm if ER and PR negative
HER-2 positive
- Fluorescent in situ hybridization (FISH) must show gene amplification
- IHC assay must show a strong positive (3+) staining score
- Ductal carcinoma in situ (DCIS) components must not be counted in determination of the degree of IHC staining or FISH amplification
No locally advanced (T4) tumors at diagnosis, including:
- Tumors fixed to chest wall
- Peau d'orange
- Skin ulcerations/nodules
- Clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
No bilateral invasive carcinoma or DCIS (metachronous or synchronous)
- Unilateral invasive carcinoma and previous metachronous or synchronous DCISof the contralateral breast treated with mastectomy allowed
- No prior breast cancer except lobular carcinoma in situ (LCIS)
No more than 84 days since prior mastectomy or axillary or sentinel node dissection
- No gross or microscopic disease at margins
- No significant pericardial effusion
Hormone receptor status:
- ER/PR status known
- Female
- Any status
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST no greater than 2 times ULN
- LVEF normal
- No prior myocardial infarction or congestive heart failure
- No prior arrhythmia or cardiovalvular disease that requires medications or is clinically significant
- No uncontrolled hypertension (diastolic blood pressure [BP] greater than 100 mm Hg and systolic BP greater than 200 mm Hg)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 2 months after study participation
- No active unresolved infection
- No known sensitivity to benzyl alcohol
- No grade 2 or greater neuropathy
No other prior malignancy within the past 5 years except:
- Effectively treated squamous cell or basal cell skin cancer
- Carcinoma in situ of the cervix treated with surgery only
- LCIS of the ipsilateral or contralateral breast treated with surgery and/or tamoxifen only
- No prior biologic therapy or immunotherapy for breast cancer
- No prior chemotherapy for breast cancer
- No prior anthracycline or taxane
- Prior tamoxifen or any other hormonal therapy for breast cancer allowed if administered for no more than 4 weeks
- Prior tamoxifen or raloxifene for chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (e.g., prior LCIS) allowed
- No concurrent tamoxifen or raloxifene
- No concurrent hormonal therapy (e.g., birth control pills or hormone replacement therapy)
- No prior radiotherapy for breast cancer
- See Disease Characteristics
- No concurrent digitalis or beta-blockers for congestive heart failure
- No concurrent medications for cardiac arrhythmias or angina pectoris
- No concurrent cardioprotective drugs
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005970
Locations
| United States, Minnesota | |
| North Central Cancer Treatment Group | |
| Rochester, Minnesota, United States, 55905 | |
Sponsors and Collaborators
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Southwest Oncology Group
Investigators
| Principal Investigator: | Edith Perez | North Central Cancer Treatment Group |
More Information
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00005970 History of Changes |
| Other Study ID Numbers: | NCI-2012-01849, NCCTG-N9831, U10CA025224, CDR0000067953 |
| Study First Received: | July 5, 2000 |
| Last Updated: | January 14, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Trastuzumab Doxorubicin Tamoxifen Paclitaxel Aromatase Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Antineoplastic Agents, Hormonal Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Bone Density Conservation Agents Estrogen Antagonists |
ClinicalTrials.gov processed this record on May 16, 2013