Know Cancer

forgot password

Phase I Study of Tipifarnib (IND# 58359, R115777) and Sorafenib (IND# 69896, BAY 43-9006) in Patients With Biopsiable Advanced Cancers

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Phase I Study of Tipifarnib (IND# 58359, R115777) and Sorafenib (IND# 69896, BAY 43-9006) in Patients With Biopsiable Advanced Cancers


I. To evaluate the safety and toxicity and to determine MTD of tipifarnib in combination
with sorafenib.


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 RPPA analysis.

OUTLINE: This is a dose-escalation study of tipifarnib.

Patients receive oral sorafenib once or twice daily or every other day for 28 days and oral
tipifarnib once or twice daily for 21 days. Treatment repeats every 28 days for 12 courses
in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks.

Inclusion Criteria:

- Patients must have had =< 4 prior chemotherapy regimens

- Patients must have advanced cancer that is refractory to standard therapy or for
whom there is no standard therapy that increases survival by three months

- ECOG performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 12 weeks

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< 1.5

- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

- Creatinine within normal institutional limits OR - creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (a
calculated CrCL is acceptable)

- INR/PT =< within institutional guidelines for biopsy procedures ( =< 16 seconds)

- Eligibility of patients receiving any other medications or substances known to affect
or with the potential to affect the activity or pharmacokinetics of BAY 43-9006 or
R115777 will be determined following review of their case by the Principal

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

- Ability to understand and the willingness to sign a written informed consent document

- Tumor accessible for repeat biopsies

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any investigational agents other than BAY 43-9006 and

- Patients with known brain metastases are excluded except for patients who have had
treated brain metastases and are currently not taking anti-seizure medications or

- Patients may not have allergies to imidazoles (e.g., clotrimazole, ketoconazole,
miconazole, econazole) or a history of allergic reactions attributed to any other
compound of similar chemical or biologic composition to either BAY 43-9006 or R115777

- Uncontrolled hypertension with systolic blood pressure of >140 mmHg or diastolic
pressure >90 mmHg; however, patients with well-controlled hypertension are eligible

- Patients must not have any evidence of current history of bleeding diathesis

- Patients may not have grade 2 or greater peripheral neuropathy

- Patients with any condition that impairs their ability to swallow pills are excluded

- Patients cannot be receiving EIAEDs (e.g., phenytoin, carbamazepine, phenobarbital)
nor any other CYP3A4 inducer such as rifampin or St. John's wort

- Uncontrolled intercurrent illness including, but not limited to, uncontrolled
hypertension, ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements

- Patients with a NYHA classification >2

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated

- HIV-positive patients on combination antiretroviral therapy are ineligible

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of tipifarnib in combination with sorafenib determined by dose limiting toxicities

Outcome Description:

Descriptive statistics and graphical analysis will be used to summarize the data. Categorical variables will be summarized in frequency tables.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

David Hong

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2005

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



M D Anderson Cancer Center Houston, Texas  77030