Cisplatin and Paclitaxel With or Without Everolimus in Treating Patients With Stage II or Stage III Breast Cancer
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase II Neo-Adjuvant Study of Cisplatin, Paclitaxel With or Without RAD001 in Patients With Triple-negative Locally Advanced Breast Cancer.|
- Pathological complete response [ Time Frame: at time of surgery, week 15-18 ] [ Designated as safety issue: No ]Pathological complete response is defined as no residual tumor on histopathological analysis of both breast and axillary contents.
- Number of patients that underwent breast conservation surgery [ Time Frame: at the time of surgery, week 15-18 ] [ Designated as safety issue: No ]Defined as patients who did not undergo complete removal of their cancerous breast (mastectomy).
- Clinical tumor response to neoadjuvant therapy as measured by ultrasound immediately before surgery [ Time Frame: After treatment, week 12-15 ] [ Designated as safety issue: No ]Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
- Number of Patients With Each Worst-grade Toxicity Response [ Time Frame: week 12 ] [ Designated as safety issue: Yes ]Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe to grade 5, most severe) following NCI Common Toxicity Criteria. Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables.
- Therapy-mediated changes in cell cycle position, proliferation, and apoptosis as well as status, levels, and phosphorylation state of p53, p73, and p63 and select p53 family target genes [ Time Frame: Before treatment, on day 3-5 of week 1, and at week 12 ] [ Designated as safety issue: No ]To determine the relevance of pathway modulation in triple negative breast cancer cell networking
- Ability of p63 and p73 gene signatures to predict patient response [ Time Frame: Before treatment, on day 3-5 of week 1, and at week 12 ] [ Designated as safety issue: No ]To determine the levels of P63 and p73 in order to correlate these levels with patient response to treatment to help define a biomarker signature associated with p63/p73 dependence in triple negative breast cancers
|Study Start Date:||June 2009|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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
Given IVDrug: everolimus
Given orallyDrug: paclitaxel
Active Comparator: Arm II
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
Given IVDrug: paclitaxel
Given IVOther: placebo
- 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.
- 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.
|Contact: Vanderbilt-Ingram Cancer Center Clinical Trials Office||800-811-8480|
|United States, Alabama|
|University of Alabama||Recruiting|
|Birmingham, Alabama, United States, 35249|
|Contact: Clinical Trials Office 205-934-2084|
|Principal Investigator: John Carpenter, MD|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: clinical trials 617-632-2335|
|Principal Investigator: Erica Mayer, MD, MPH|
|United States, Mississippi|
|University of Mississippi Medical Center Research Institute||Recruiting|
|Jackson, Mississippi, United States, 39213|
|Contact: clinical trials 601-815-4540|
|Principal Investigator: Barbara Craft, MD|
|United States, Pennsylvania|
|Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033|
|Contact: clinical trials 717-531-8678|
|Principal Investigator: Cristina Truica, MD|
|United States, Tennessee|
|MBCCOP - Meharry Medical College - Nashville||Terminated|
|Nashville, Tennessee, United States, 37208|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Recruiting|
|Nashville, Tennessee, United States, 37064|
|Contact: VICC Clinical Trials Information Program 800-811-8480|
|Principal Investigator: Ingrid Mayer, MD|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232-6838|
|Contact: Clinical Trials Office - Vanderbilt-Ingram Cancer Center 800-811-8480|
|Principal Investigator: Ingrid Mayer, MD|
|United States, Texas|
|The Methodist Hospital Research Institute||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Amber Froehlich 713-441-0629|
|Principal Investigator: Jenny Chang, MD|
|United States, Virginia|
|University of Virginia Health Sciences Center||Recruiting|
|Charlottesville, Virginia, United States, 22098|
|Contact: clinica trials 434-982-1495|
|Principal Investigator: Patrick Dillon, MD|
|Principal Investigator:||Ingrid Mayer, M.D.||Vanderbilt-Ingram Cancer Center|