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Study Summary
No. 2005-0363:.......Advanced Cancers......David S. Hong......Phase I Program
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Study Summary Title
Study Summary
Number:
2005-0363
Study Title:PHASE I STUDY OF TIPIFARNIB (IND#58359, R115777) AND SORAFENIB (IND#69896, BAY 43-9006) IN PATIENTS WITH BIOPSIABLE ADVANCED CANCERS
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Physician New Patient Referral
Name:David S. HongPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Phase I ProgramReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1226
Contact us about clinical trials
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General Information
Disease Group:Advanced CancersSupported By:N/A
Phase of Study:Phase IReturn
Visit:
At least 5 times in the first 12 weeks of the study
Treatment
Agents:
BAY 43-9006
R115777
Home Care:Patients may take tipifarnib and sorafenib at home
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
None
Description/
Intervention:
The goal of this clinical research study is to find the highest dose of the
drug tipifarnib (R115777) that can be given in combination with sorafenib (BAY
43-9006) to patients with advanced cancer. The safety and effectiveness of
this study drug will also be studied.
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Study Objectives / Outcomes
Primary objectives:

To define the phase II dose:
  • To evaluate the safety and toxicity and to determine MTD of tipifarnib in combination with sorafenib.
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Secondary objectives:
  • Preliminary assessment of tipifarnib and sorafenib efficacy (objective response).
  • To determine signaling pathway profiles of patients treated with tipifarnib and sorafenib who are amenable to biopsy by RPPA analysis.
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Study Status Information
Study Activation / Registration Date:10/19/2005
IRB Review and Approval Date:07/06/2005
Study Type:Therapeutic
Recruitment Status:Closed
Projected Accrual:N/A
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) 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

2) Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of BAY 43-9006 in combination with R115777 in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.

3) ECOG performance status </= 2 (Karnofsky >/= 60%).

4) Life expectancy of greater than 12 weeks

5) Patients must have normal organ and marrow function as defined below: (1) leukocytes >/= 3,000/mcL; (2) absolute neutrophil count >/= 1,500/mcL; (3) platelets >/= 100,000/mcL; (4) total bilirubin </= 1.5 ; (5) T(SGOT)/ALT(SGPT) </= 2.5 X institutional upper limit of normal; (6) 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); (7) INR/PT </= within institutional guidelines for biopsy procedures (</= 16 seconds).

6) 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 Investigator

7) The effects of BAY 43-9006 and R115777 on the developing human fetus are unknown. For this reason and because other tyrosine kinase inhibitors and farnesyl transferase inhibitors are known to be teratogenic, 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

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

9) Tumor accessible for repeat biopsies

Exclusion Criteria:1) 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.

2) Patients may not be receiving any investigational agents other than BAY 43-9006 and R115777

3) 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 steroids.

4) 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

5) Uncontrolled hypertension with systolic blood pressure of >140 mmHg or diastolic pressure >90 mmHg. However, patients with well-controlled hypertension are eligible

6) Patients must not have any evidence of current history of bleeding diathesis.

7) Patients may not have grade 2 or greater peripheral neuropathy

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

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

10) 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

11) Patients with a NYHA classification >2

12) Pregnant women are excluded from this study because BAY 43-9006 is a tyrosine kinase inhibitor and R115777 is a farnesyl transferase inhibitor, both of which have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 43-9006 or R115777, breastfeeding should be discontinued if the mother is treated with either of these agents

13) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with BAY 43-9006 and/or R115777. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

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Links
Registration Number: NCT00244972
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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