Clinical trial NCT00295893: Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer
Official title: Randomized Phase II Study of Docetaxel, Adriamycin, and Cytoxan (TAC) Versus Adriamycin/Cytoxan, Followed by Abraxane/Carboplatin (ACAC) +/- Trastuzumab as Neoadjuvant Therapy for Patients With Stage II-III Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: inflammatory breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
male breast cancer
Paget disease of the breast with invasive ductal carcinoma
invasive ductal breast carcinoma with predominant intraductal component
invasive ductal breast carcinoma
medullary ductal breast carcinoma with lymphocytic infiltrate
comedo ductal breast carcinoma
invasive lobular breast carcinoma with predominant in situ component
invasive lobular breast carcinoma
mucinous ductal breast carcinoma
papillary ductal breast carcinoma
tubular ductal breast carcinoma
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-24
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.

PURPOSE: This randomized phase II trial is comparing two different regimens of combination chemotherapy given together with or without trastuzumab to see how well they work in treating patients with stage II or stage III breast cancer.

Detailed description: OBJECTIVES:

Primary

* Compare 2 neoadjuvant chemotherapy regimens (docetaxel, doxorubicin hydrochloride, and cyclophosphamide \[TAC\] vs doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin \[ACAC\]), in terms of toxicities and effectiveness as defined by the pathological complete remission rate, in patients with non HER2/neu overexpressing stage II or III breast cancer.
* Evaluate the probability of achieving a pathological complete remission when adding trastuzumab (Herceptin®) to ACAC in the subset of patients with HER2/neu overexpressing stage II or III breast cancer.

Secondary

* Identify prognostic and predictive markers of outcome, recurrence, and targets of therapy.

OUTLINE: This is a randomized study. Patients with non HER2/neu overexpressing tumors are randomized to 1 of 2 treatment arms. Patients with HER2/neu overexpressing tumors are assigned to arm III.

* Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses.
* Arm II: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses.
* Arm III: Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin.

Within 4 weeks after completion of chemotherapy with or without trastuzumab (Herceptin®), all patients undergo surgery.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven infiltrating ductal or lobular breast carcinoma

  * Stage II or III disease
  * Inflammatory breast cancer allowed
* Hormone-receptor status not specified

PATIENT CHARACTERISTICS:

* ECOG performance status \< 2
* Male or female
* Menopausal status not specified (for female patients)
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Bilirubin normal (except for patient's with Gilbert's disease)
* Creatinine ≤ 1.2 mg/dL
* Creatinine clearance ≥ 70 mL/min
* Ejection fraction ≥ 50% on MUGA
* No neuropathy ≥ grade 1
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective nonhormonal contraception
* No prior malignant disease within the past 5 years, excluding:

  * Squamous cell or basal cell skin carcinoma
  * Stage I or in situ cervical carcinoma
* No noninvasive (in situ) breast carcinoma within the past 5 years

PRIOR CONCURRENT THERAPY:

* At least 5 years since prior antiestrogen treatment for any indication other than breast cancer prevention (tamoxifen, raloxifene, or an aromatase inhibitor)
* No prior radiotherapy to the chest wall

Primary outcomes:
measure: Count of Patients With Pathologic Complete Response (pCR)
timeFrame: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months
measure: Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1.
timeFrame: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Joanne Mortimer, MD
role: PRINCIPAL_INVESTIGATOR
References: