Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as vorinostat and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat and capecitabine in treating patients with unresectable or metastatic solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Capecitabine in Patients With Solid Tumors|
- Maximum tolerated doses of vorinostat (SAHA) and capecitabine [ Time Frame: 1 cycle ] [ Designated as safety issue: Yes ]
- Safety and tolerability as assessed by CTCAE v3.0 [ Time Frame: All cycles ] [ Designated as safety issue: Yes ]
- Response rate as assessed by RECIST criteria [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
- Molecular markers as assessed by molecular analysis [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
- Survival [ Time Frame: progression free survival every 2 cycles ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
|Experimental: SAHA (Suberoylanilide Acid) with Capecitabine||Drug: capecitabine Drug: vorinostat|
- Determine the maximum tolerated dose and recommended phase II dose of vorinostat (SAHA) and capecitabine in patients with metastatic or unresectable solid tumors.
- Determine the safety and tolerability of this regimen in these patients.
- Correlate the clinical effects with the pharmacokinetic effects of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive oral vorinostat (SAHA) once or twice daily and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses beyond documentation of CR. Patients achieving a partial response receive 2 courses beyond documentation of best response.
Cohorts of 3-6 patients receive escalating doses of SAHA and capecitabine 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. An additional 12 patients are treated at the MTD.
After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter.
PROJECTED ACCRUAL: Approximately 18-30 patients will be accrued for this study within 6-10 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00121277
|Ottawa Hospital Regional Cancer Centre - General Campus|
|Ottawa, Ontario, Canada, K1H 8L6|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Eric X. Chen, MD, PhD||Princess Margaret Hospital, Canada|