Everolimus and Bortezomib in Treating Patients With Relapsed or Refractory Lymphoma
RATIONALE: Everolimus and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with bortezomib in treating patients with relapsed or refractory lymphoma.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Trial of the Combination of Everolimus (RAD001) and Bortezomib (VELCADE) for Relapsed or Refractory Lymphoma|
- Maximum tolerated dose of everolimus in combination with bortezomib [ Time Frame: after 1 course (21 days) ] [ Designated as safety issue: Yes ]Defined as the highest dose level at which 0 out of 3, or 1 out of 6, subjects experiences dose-limiting toxicity (DLT).
- Frequency counts and percentage of patients experiencing toxicities [ Time Frame: After 1 course (21 days) ] [ Designated as safety issue: Yes ]Adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
- Pharmacokinetics [ Time Frame: after 1 course (21 days) ] [ Designated as safety issue: No ]
- Response rate [ Time Frame: Every 3 courses (9 weeks) for the first 12 courses, after 5th restaging scan every 6 courses (18 weeks) until off study ] [ Designated as safety issue: No ]Response assessment will use response definitions of the International Working Group (2007 guidelines). Estimated with exact 95% confidence intervals.
- 6-month progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Correlation of tumor characteristics with response to treatment [ Time Frame: after one course (21 days) ] [ Designated as safety issue: No ]Exploratory analyses will be done using logistic regression to assess associations between tumor characteristics or biomarkers and response.
|Study Start Date:||June 2008|
|Estimated Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Everolimus and Bortezomib
Patients will receive a combination of Everolimus by mouth and Bortezomib intravenously for a 21 day cycle.
Drug: Bortezomib (IV) and Everolimus (PO)
Patients will be assigned to one of the following dose levels of Bortezomib: 0.7mg/m2, 1.0 mg/m2, or 1.3mg/m2 in combination with Everolimus (PO) (5mg every other day, 5mg daily, or 10mg daily).
Patients will be assigned to one of the following dose levels of Everolimus: 5mg every other day, 5mg daily, or 10mg daily in combination with Bortezomib (IV) (on days 1,4,8, and 11 of a 21 day cycle).
- Determine the maximum tolerated dose of everolimus (up to 10 mg PO daily) in combination with bortezomib in patients with relapsed/refractory indolent or mantle cell non-Hodgkin's lymphoma (NHL) including cutaneous forms, or relapsed/refractory aggressive NHL ineligible for hematopoetic stem cell transplantation
- Evaluate the toxicity of this combination.
- Assess the pharmacokinetics interactions between these agents.
- Assess the response rate and 6-month progression-free survival in treated patients.
- Obtain preliminary data to assess associations between tumor characteristics and response to treatment. in those subjects who underwent biopsy prior to study treatment.
OUTLINE: This is a dose-escalation study.
Patients receive bortezomib IV on days 1, 4, 8, and 11. Patients also receive oral everolimus once daily or once every other day on days 1-21 in all courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients will undergo blood sample collection on Cycle 1, Day 11 for pharmacokinetic studies. Baseline tumor expression of mTOR and NFkB -related proteins (i.e., pS6K, pAKT, and cREL) and FOXP3 is assessed by immunohistochemistry.
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Brian Hill, MD 216-444-6833 firstname.lastname@example.org|
|Principal Investigator:||Brian Hill, MD, PhD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|