Clinical trial NCT00930930
Conditions: Breast Cancer
Keywords: triple-negative breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer male breast cancer
Sponsor: Vanderbilt-Ingram Cancer Center
Start date: 2009-06-01; Completion date: 2014-10-01
Enrollment: 145 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving chemotherapy together with everolimus 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 cisplatin and paclitaxel are more effective when given together with or without everolimus in treating patients with breast cancer.

PURPOSE: This randomized phase II trial is studying how well cisplatin and paclitaxel work when given together with or without everolimus in treating patients with stage II or stage III breast cancer.

Detailed description:
OBJECTIVES:

Primary

* To determine the pathological complete response in patients with triple-negative, stage II or III breast cancer treated with neoadjuvant cisplatin and paclitaxel with or without everolimus.

Secondary

* To determine the safety profile of these treatment regimens.
* To evaluate tumor response to these treatment regimens as measured by ultrasound before definitive surgery.
* To evaluate the rate of breast conservation surgery after treatment with these regimens.
* To determine treatment-mediated changes in cell cycle position, proliferation, and apoptosis as well as status, levels, and phosphorylation state of S6K, p53, p73, and p63 and select p53 family target genes before and after initiation of paclitaxel.
* To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to identify a pre-treatment gene signature that will predict response.
* To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to identify a change in gene signature after the first treatment that will predict response.
* To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if previously established p63 and p73 gene signatures predict response to treatment.
* To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if a change will be observed in p63 and p73 gene signatures between pre- and post-treatment biopsies.
* To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if triple-negative breast cancers can be clustered into different subtypes on the basis of gene expression, given the size of the microarray data set that will be generated from this clinical trial and previous clinical trials (\> 100 tumors).
* To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if p63 and p73 gene signatures can sub-classify triple-negative breast cancers.

OUTLINE: This is a multicenter study. Patients are stratified according to initial lymph node status (positive vs negative involvement) and tumor grade (low or intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive cisplatin IV over 1 hour and oral everolimus once weekly in weeks 1-12 and paclitaxel IV over 1 hour once weekly in weeks 4-12 in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive cisplatin IV over 1 hour and oral placebo once weekly in weeks 1-12 and paclitaxel IV over 1 hour once weekly in weeks 4-12 in the absence of disease progression or unacceptable toxicity.

Approximately 3-6 weeks after the completion of neoadjuvant therapy, patients undergo partial or total mastectomy with lymph node evaluation. Patients may then receive additional chemotherapy or radiotherapy.

Patients undergo ultrasound-guided core biopsies at baseline and in weeks 1, 4, and 12 for analysis of proliferation, apoptosis, and pathway activity markers via IHC or western blotting and RNA microarrays.

Patients are followed up within 3 weeks after surgery.

Arms: arm 1: Cisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks arm 2: Cisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks
Interventions: intervention 1: cisplatin intervention 2: everolimus intervention 3: paclitaxel intervention 4: placebo intervention 5: Venous blood draw
Intervention descriptions: intervention 1: Given IV intervention 2: Given orally intervention 3: Given IV intervention 4: Given orally intervention 5: Venous blood (2-3 tablespoons) will be taken for germline DNA analysis to complement the correlative studies in the tumor tissue. Blood can be drawn at any time prior, during, or after completion of study treatment

Protocol documents: