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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00244972
First received: October 25, 2005
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

This phase I trial is studying the side effects and best dose of tipifarnib when given together with sorafenib in treating patients with advanced cancer. Tipifarnib and sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sorafenib tosylate
Drug: tipifarnib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Tipifarnib (IND# 58359, R115777) and Sorafenib (IND# 69896, BAY 43-9006) in Patients With Biopsiable Advanced Cancers

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of tipifarnib in combination with sorafenib determined by dose limiting toxicities [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Descriptive statistics and graphical analysis will be used to summarize the data. Categorical variables will be summarized in frequency tables.


Secondary Outcome Measures:
  • Clinical response evaluated using RECIST criteria [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics and graphical analysis will be used to summarize the data. For continuous variables, we will use the mean (standard deviation) or median (range) to summarize outcomes.


Enrollment: 74
Study Start Date: October 2005
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tipifarnib, sorafenib tosylate)
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.
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 Investigator
  • 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 R115777
  • 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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00244972

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: David Hong M.D. Anderson Cancer Center
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00244972     History of Changes
Other Study ID Numbers: NCI-2009-00132, NCI-2009-00132, 2005-0363, CDR0000446569, 2005-0363, 7156, P30CA016672, U01CA062461
Study First Received: October 25, 2005
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Tipifarnib
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014