Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors (PTK/RAD)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00303732|
Recruitment Status : Completed
First Posted : March 17, 2006
Last Update Posted : March 3, 2016
RATIONALE: Vatalanib and everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib and everolimus and to see how well they work in treating patients with advanced solid tumors.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Cancer Unspecified Adult Solid Tumor, Protocol Specific||Drug: RAD001 (everolimus) Drug: PTK787 (vatalanib)||Phase 1|
- Determine the maximum tolerated dose (MTD) of vatalanib and everolimus in patients with advanced solid tumors.
- Determine the safety and tolerability of vatalanib and everolimus in patients with advanced solid tumors.
- Evaluate the safety and tolerability of vatalanib and everolimus at the MTD in patients with metastatic renal cell carcinoma (RCC).
- Describe the non dose-limiting toxic effects associated with vatalanib and everolimus.
- Describe the pharmacokinetics of vatalanib and everolimus in patients with advanced solid tumors.
- Determine the functional extent of mTOR inhibition by changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells in patients treated with vatalanib and everolimus.
- Describe any clinical responses seen in patients with metastatic RCC in a dose-expansion cohort treated at the MTD.
- Observe overall survival of RCC patients treated with vatalanib and everolimus.
- Determine the time to progression of patients with RCC treated with vatalanib and everolimus.
OUTLINE: This is a phase I dose-escalation study followed by a phase Ib study.
- Phase I (solid tumors): Patients receive oral vatalanib on days 1-28 and oral everolimus on days 15-28 during course 1 and on days 1-28 during all subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of vatalanib and everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase Ib (renal cell carcinoma only): Patients receive oral vatalanib and oral everolimus at the MTD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||PTK787/ZK222584 and RAD001 for Patients With Advanced Solid Tumors|
|Study Start Date :||December 2004|
|Actual Primary Completion Date :||August 2010|
|Actual Study Completion Date :||August 2012|
Experimental: PTK787, RAD001
PTK787 (vatalinib) 1000 mg daily, RAD001 (everolimus) 5 mg daily
Drug: RAD001 (everolimus)
Other Name: Afinitor
Drug: PTK787 (vatalanib)
- Maximum tolerated dose (MTD) of vatalanib and everolimus [ Time Frame: Day 1 - 28 ]Patients were evaluated on Day 1,14 and 28 for dose limiting toxicities
- Safety and tolerability [ Time Frame: Duration of study treatment ]Adverse events were assessed every 14 days for the length of the treatment period.
- Safety and tolerability at the MTD in patients with metastatic renal cell carcinoma (RCC) [ Time Frame: Duration of study treatment ]Patients were assessed for adverse events every 14 days while on study treatment
- Non dose-limiting toxicity [ Time Frame: Duration of study treatment ]Patients were assessed every 14 days for non dose-limiting toxicity while on study treatment
- Pharmacokinetics [ Time Frame: Day 14 Cycle 1, Day 1 Cycle 2 ]Blood was drawn for PK assessment on Day 14 of Cycle 1 and Day 1 of Cycle 2
- Changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells [ Time Frame: Day 1 and 28 ]Samples were collected on Day 1 and at Day 28 of Cycle 1
- Clinical response in patients with metastatic RCC [ Time Frame: Duration of treatment ]patients underwent restaging studies every 2 cycles while on treatment for evidence of disease response
- Overall survival of patients with RCC [ Time Frame: Until death ]
- Time to progression of patients with RCC [ Time Frame: Duration of study treatment ]Patients were followed for evidence of disease progression as long as they remained on study drug.
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): NCT00303732
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Daniel J. George, MD||Duke Cancer Institute|