Clinical trial NCT00524459: Pegylated Liposomal Doxorubicin and Docetaxel in Treating Women With Locally Advanced Breast Cancer That Can Be Removed By Surgery
Official title: Phase II Study of Neoadjuvant Pegylated Liposomal Doxorubicin and Docetaxel in Locally Advanced Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IIIA breast cancer
stage IIIB breast cancer
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-09-03
Enrollment: 6
Sex: FEMALE
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin and docetaxel, 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) and giving them before surgery may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving liposomal doxorubicin together with docetaxel before surgery and to see how well it works in treating women with locally advanced breast cancer that can be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To evaluate the rate of pathological complete response and clinical complete response in women with locally advanced breast cancer treated with pegylated doxorubicin hydrochloride liposome and docetaxel.

Secondary

* To assess the overall clinical local regional response in patients treated with this preoperative chemotherapy regimen.
* To evaluate the number of patients who would have required a mastectomy upfront but who underwent breast conservation therapy instead after neoadjuvant chemotherapy.
* To assess the safety, particularly with regard to neutropenia and cardiac toxicity, of pegylated doxorubicin hydrochloride liposome and docetaxel.

OUTLINE: This is a multicenter study.

Patients receive pegylated doxorubicin hydrochloride liposome IV over 90 minutes and docetaxel IV over 90 minutes on day 1. Patients receive pegylated filgrastim subcutaneously on days 2 or 3 post-chemotherapy in courses 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Within 8 weeks after completion of chemotherapy, patients undergo a lumpectomy or mastectomy to remove the tumor. Some patients may receive additional therapy after surgery, including hormonal therapy, chemotherapy, or radiotherapy.

After completion of study therapy, patients are followed periodically for up to 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed breast cancer using core biopsies

  * Locally advanced disease
  * Resectable disease
  * Fine needle aspiration cytology allowed and must demonstrate invasive adenocarcinoma
* No more than 8 weeks since initial cytologic or histologic diagnosis of breast cancer
* Tumor must meet the following criteria:

  * Palpable on clinical examination and confined to either the breast or to the breast and ipsilateral axilla
  * Measured clinically as greater than 2 cm in size (T2)
* Patients with skeletal pain are eligible if bone scan and/or roentgenological examination fail to disclose metastatic disease

  * Suspicious findings must be confirmed as benign by x-ray, MRI scan, or biopsy
* Hormonal status not specified

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Female
* Menopausal status not specified
* ECOG performance status 0-2
* Life expectancy ≥ 10 years
* Platelet count ≥ 100,000/mm³
* ANC ≥ 1,500/mm³
* Hemoglobin ≥ 9.0 g/dL
* Bilirubin normal
* AST or ALT normal
* Alkaline phosphatase normal
* Serum creatinine normal
* Negative pregnancy test
* Fertile patients must use effective contraception (e.g., abstinence, intrauterine device, barrier device with spermicide, or surgical sterilization) during and for 3 months after completion of study therapy
* Normal cardiac function by LVEF or MUGA scan
* Patients with prior non-breast malignancies are eligible if they have been disease-free for ≥ 10 years

  * The following are allowed even if diagnosed within the past 10 years:

    * Squamous or basal cell carcinoma of the skin that has been effectively treated
    * Carcinoma in situ of the cervix that has been treated by operation only
    * Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by segmental resection only

Exclusion criteria:

* Pregnant or lactating women
* Male patients
* Hyperbilirubinemia
* Female patients with 1 or more of the following conditions:

  * Ulceration, erythema, infiltration of the skin (complete fixation), or peau d'orange (edema) of any magnitude

    * Tethering or dimpling of the skin or nipple inversion should not be interpreted as skin infiltration
  * Ipsilateral lymph nodes that are clinically fixed to one another or to other structures (N2 disease)
  * Bilateral malignancy or a mass in the opposite breast suspicious for malignancy, unless there is biopsy proof that the mass is not malignant
  * Suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless there is biopsy evidence that these are not involved with the tumor
* Nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude study therapy
* Active cardiac disease that would preclude the use of doxorubicin hydrochloride, including any of the following:

  * Documented myocardial infarction
  * Angina pectoris that requires the use of antianginal medication
  * History of documented New York Heart Association class II-IV heart failure
  * Valvular disease with documented cardiac function compromise
  * Poorly controlled hypertension (i.e., diastolic BP \> 100 mm Hg)

    * Patients with well-controlled hypertension and on medication are eligible for study
* Psychiatric or addictive disorders that would preclude obtaining informed consent

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

* Concurrent noncancer therapies allowed if used for conditions other than breast cancer
* Adjuvant therapy after surgery allowed

Exclusion criteria:

* Prior radiotherapy, chemotherapy, immunotherapy, and/or hormonal therapy for breast cancer
* Prior anthracycline therapy for any condition
* Concurrent hormonal therapy including tamoxifen, aromatase inhibitors, or raloxifene
* Concurrent sex hormonal therapy including birth-control pills or ovarian hormonal replacement therapy
* Concurrent other cancer therapy
* Concurrent herbal or alternative therapies for breast cancer

Primary outcomes:
measure: Pathological Complete Response
timeFrame: Mammogram done pre-treatment and after four and six cycles of study chemotherapy treatment.
measure: Clinical Complete Response
timeFrame: Surgery done after completion of six cycles of study chemotherapy treatment.
Secondary outcomes:
measure: Overall Clinical Local Regional Response
timeFrame: Mammogram done pre-treatment and after four and six cycles of study chemotherapy treatment.
measure: Number of Women Who Would Have Required a Mastectomy Upfront But Who Underwent Breast Conservation Therapy Instead After Neoadjuvant Chemotherapy
timeFrame: Baseline (pre-treatment) surgical assessment, and post-chemotherapy surgical outcome.
measure: Safety, in Terms of Neutropenia and Cardiac Toxicity
timeFrame: Every cycle during study treatment and 8 weeks post-treatment.
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Tracey O'Connor, MD
role: PRINCIPAL_INVESTIGATOR
References: