A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic Breast Cancer
- 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
- 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
- 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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
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.
at 8 weeks
Ingrid Mayer, MD
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC BRE 0949
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|West Tennessee Cancer Center at Jackson-Madison County General Hospital||Jackson, Tennessee 38301|
|Erlanger Cancer Center at Erlanger Hospital - Baroness||Chattanooga, Tennessee 37403|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|
|Baptist Regional Cancer Center at Baptist Riverside||Knoxville, Tennessee 37901|