Tipifarnib and Sorafenib Tosylate in Treating Patients With Biopsiable Advanced Cancer
|Advanced Malignant Neoplasm||Other: Laboratory Biomarker Analysis Drug: Sorafenib Tosylate Drug: Tipifarnib||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Study of Tipifarnib (R115777) and Sorafenib (BAY 43-9006) in Patients With Biopsiable Advanced Cancers|
- MTD defined as the highest dose level in which fewer than 2 patients experience a dose limiting toxicity as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ]Descriptive statistics and graphical analysis will be used to summarize the data. Categorical variables will be summarized in frequency tables.
- Clinical response evaluated using Response Evaluation Criteria In Solid Tumors criteria [ Time Frame: Up to 4 weeks ]Descriptive statistics and graphical analysis will be used to summarize the data. For continuous variables, mean (standard deviation) or median (range) will be used to summarize outcomes.
- Signaling pathway inhibition in tumor tissue by RPPA [ Time Frame: Up to 4 weeks ]The analysis of the activated signaling pathways using Pathway Analysis (Ingenuity) will determine whether particular molecular profiles are likely to respond to tipifarnib and sorafenib.
|Study Start Date:||October 2005|
|Study Completion Date:||March 2017|
|Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate, tipifarnib)
Patients receive sorafenib tosylate PO QD or BID on days 1-28 and tipifarnib PO QD or BID on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients may be allowed to continue the treatment after the 12 courses if there is continued clinical response or disease stabilization, and patients do not have significant toxicities.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Sorafenib Tosylate
Other Names:Drug: Tipifarnib
I. To evaluate the safety and toxicity and to determine maximum tolerated dose (MTD) of tipifarnib in combination with sorafenib (sorafenib tosylate).
I. Preliminary assessment of tipifarnib and sorafenib efficacy (objective response).
II. To determine signaling pathway profiles of patients treated with tipifarnib and sorafenib who are amenable to biopsy by reverse phase protein microarray (RPPA) analysis.
OUTLINE: This is a dose-escalation study of tipifarnib.
Patients receive sorafenib tosylate orally (PO) once daily (QD) or twice daily (BID) on days 1-28 and tipifarnib PO QD or BID on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients may be allowed to continue the treatment after the 12 courses if there is continued clinical response or disease stabilization, and patients do not have significant toxicities.
After completion of study treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00244972
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||David Hong||M.D. Anderson Cancer Center|