First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
Transitional Cell Carcinoma
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Everolimus or Everolimus Plus Paclitaxel as First-line Therapy in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma: Hoosier Cancer Research Network GU10-147|
- Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]To evaluate clinical benefit rate (complete response, partial response, and stable disease) at 4 months from initiation of treatment.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]To determine the safety of everolimus and everolimus plus paclitaxel in this patient population.
- Progression Free Survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]To determine progression free survival
- Survival - 1 year [ Time Frame: 12 months ] [ Designated as safety issue: No ]To determine survival at 1-year from the initiation of treatment.
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Cohort 1
Single-agent everolimus (enrollment limited to patients with patients with creatinine clearance < 60 ml/min AND Karnofsky performance status of 60-70%)
10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.
Active Comparator: Cohort 2
Everolimus plus paclitaxel (enrollment limited to patients with creatinine clearance < 60 ml/min OR Karnofsky performance status of 60-70%)
10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.Drug: Paclitaxel
Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
OUTLINE: This is a multi-center study
Patients will be enrolled into one of two parallel cohorts:
- Cohort 1: impaired renal function AND poor performance status (cycle length = 28 days). Everolimus 10 mg orally daily
- Cohort 2: impaired renal function OR poor performance status (cycle length = 28 days). Everolimus 10 mg orally daily + IV Paclitaxel 80 mg/m2 on D1, 8, 15
Restaging evaluations will be performed after every 2 cycles.
Treatment will continue until disease progression or unacceptable toxicity.
Karnofsky performance status 60-70%
Life Expectancy: Not specified
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 100 K/mm3
- INR ≤ 1.5 (Anticoagulants are allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of Low molecular weight (LMW) heparin for at least 2 weeks prior to registration for protocol therapy).
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L
- Fasting triglycerides ≤ 2.5 x ULN.
- Fasting serum glucose < 1.5 x ULN
- Bilirubin ≤ 1.5 x ULN
- Aminotransferases (AST and ALT) ≤ 2.5 x ULN (unless liver metastases, then ≤ 5 x ULN)
- Calculated creatinine clearance of < 60 using the Cockcroft-Gault formula
- No symptomatic congestive heart failure of New York heart Association Class III or IV.
- No unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01215136
|United States, Alabama|
|University of Alabama Hematology Oncology Clinic at Medical West|
|Birmingham, Alabama, United States, 35294|
|United States, Illinois|
|Northwestern University, Robert H. Lurie Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60611|
|United States, Indiana|
|Cancer Care Center of Southern Indiana|
|Bloomington, Indiana, United States, 47403|
|IU Health Central Indiana Cancer Centers|
|Indianapolis, Indiana, United States, 46219|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Michigan|
|Metro Health Cancer Care|
|Wyoming, Michigan, United States, 49519|
|United States, Nebraska|
|Nebraska Cancer Specialists|
|Omaha, Nebraska, United States, 68114|
|United States, New York|
|Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center|
|New York, New York, United States, 10029|
|United States, South Carolina|
|MUSC Hollings Cancer Center|
|Charleston, South Carolina, United States, 29425|
|United States, Texas|
|University of Texas Medical Branch|
|Galveston, Texas, United States, 77555|
|United States, Virginia|
|Virginia Oncology Associates|
|Norfolk, Virginia, United States, 23502|
|Study Chair:||Matthew Galsky, M.D.||Hoosier Cancer Research Network|