Cisplatin, Paclitaxel, and Everolimus in Treating Patients With Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01031446|
Recruitment Status : Active, not recruiting
First Posted : December 14, 2009
Results First Posted : March 11, 2013
Last Update Posted : August 24, 2017
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 cisplatin and paclitaxel together with everolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: cisplatin Drug: everolimus Drug: paclitaxel Other: laboratory biomarker analysis||Phase 1 Phase 2|
- Safety profile of cisplatin, paclitaxel, and everolimus (RAD001) in patients with metastatic breast cancer. (Phase I)
- Progression-free survival (Phase II)
- Overall response rate
- Time to progression
- Number of patients with worst-grade toxicities Tertiary
- To determine p53, p63, p73, and phosphatase and tensin homolog (PTEN) levels by immunohistochemistry (IHC).
- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks.
- To correlate IHC results with clinical outcome and with the different subtypes of breast cancer determined by molecular classification (basal-type vs luminal A vs luminal B) based on microarrays of RNA extracted from formalin-fixed paraffin-embedded blocks.
- To generate microarrays of RNA extracted from fresh-frozen core biopsies (when available) to identify a pretreatment gene signature that mirrors the established p63 and p73 gene signatures that predict response to treatment.
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once daily on days 1-28 and cisplatin IV over 1 hour and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples are collected at baseline for correlative studies.
After completion of study treatment, patients are followed up at 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic Breast Cancer|
|Study Start Date :||October 2009|
|Actual Primary Completion Date :||December 2011|
|Estimated Study Completion Date :||July 2018|
Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.Drug: everolimus
Taken daily by mouth.Drug: paclitaxel
Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.Other: laboratory biomarker analysis
- Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer [ Time Frame: at 8 weeks ]The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
- Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer [ Time Frame: at 8 weeks ]The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy
- Patients With Progression-free Survival [ Time Frame: at 6 months ]Patients who had not experienced disease progression and who were alive at 6 months after study entry
- Patients With Overall Response [ Time Frame: every 12 weeks ]Per Response Evaluation Criteria in Solid Tumor (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
- Time to Progression [ Time Frame: Up to 64 weeks ]Duration in months from date on-study to date patient exhibited progressive disease
- Time to Progression in Patients With Metastatic Basal-like Breast Cancer. [ Time Frame: Up to 64 weeks ]Median duration in months from on-study to disease progression in patients with metastatic basal-like breast cancer. All patients with basal-like breast cancer are negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01031446
|United States, Tennessee|
|Erlanger Cancer Center at Erlanger Hospital - Baroness|
|Chattanooga, Tennessee, United States, 37403|
|West Tennessee Cancer Center at Jackson-Madison County General Hospital|
|Jackson, Tennessee, United States, 38301|
|Baptist Regional Cancer Center at Baptist Riverside|
|Knoxville, Tennessee, United States, 37901|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Principal Investigator:||Ingrid Mayer, MD||Vanderbilt-Ingram Cancer Center|