Tipifarnib and Erlotinib Hydrochloride in Treating Patients With Advanced Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00085553
First received: June 10, 2004
Last updated: August 22, 2014
Last verified: July 2014
  Purpose

This phase I trial studies the side effects and best dose of tipifarnib and erlotinib hydrochloride in treating patients with solid tumors that have spread to other places in the body. Tipifarnib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: erlotinib hydrochloride
Drug: tipifarnib
Other: laboratory biomarker analysis
Other: pharmacological study
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 Trial of R115777 and OSI-774 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number and severity of all adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 30 days after last study treatment ] [ Designated as safety issue: Yes ]
    Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.


Secondary Outcome Measures:
  • Best response as assessed by the Response Evaluation Criteria in Solid Tumors [ Time Frame: Start of the treatment until disease progression/recurrence, assessed up to 3 months ] [ Designated as safety issue: No ]
  • Time until any treatment related toxicity [ Time Frame: Up to 30 days after last study treatment ] [ Designated as safety issue: Yes ]
  • Time until treatment related grade 3+ toxicity [ Time Frame: Up to 30 days after last study treatment ] [ Designated as safety issue: Yes ]
  • Time until hematologic nadirs (white blood cells, ANC, platelets) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Inhibition of EGFR from tumor biopsies [ Time Frame: Up to day 21 of course 1 ] [ Designated as safety issue: No ]
    Any change in these measures will be summarized descriptively within each patient and as whole group.

  • Inhibition of FT from tumor biopsies [ Time Frame: Up to day 21 of course 1 ] [ Designated as safety issue: No ]
    Any change in these measures will be summarized descriptively within each patient and as whole group.

  • Incidence of any genetic polymorphisms [ Time Frame: Up to day 21 of course 1 ] [ Designated as safety issue: No ]
    Assessed and summarized descriptively in those patients treated at the MTD.


Enrollment: 29
Study Start Date: May 2004
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (erlotinib hydrochloride, tipifarnib)
Patients receive erlotinib hydrochloride PO QD on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximal tolerated dose of R115777 (tipifarnib) in combination with OSI-774 (erlotinib hydrochloride).

II. To describe the toxicity profile of this combination. III. To evaluate the effect of OSI-774 on the disposition of R115777. IV. To evaluate in vitro markers of farnesyl transferase (FT) inhibition and epidermal growth factor receptor (EGFR) inhibition.

OUTLINE: This is a dose-escalation study.

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)

After completion of study treatment, patients are followed up at 3 months.

  Eligibility

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

Inclusion Criteria:

  • Histologic proof of cancer that is unresectable and for which no standard life-prolonging therapy is available
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet count (PLT) >= 100,000/uL
  • Total bilirubin =< 2 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Creatinine =< 1.5 times ULN
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic Rochester for follow up
  • Life expectancy >= 12 weeks
  • At maximum tolerated dose (MTD) only: tumor that is amenable for serial biopsy
  • Medically capable and willing to provide the biologic specimens as required by the protocol Note: The goals of this study include assessment of the biologic effects on surrogate markers of the agent(s) being tested and are, therefore, contingent upon availability of the biologic specimens; patients with pre-existing clinical contraindications (e.g. anticoagulant therapy) for biopsy will be excluded from participation in the study; however, those patients who develop a major complication associated with the first biopsy (e.g. bleeding) or who develop clinical contraindications (e.g., anticoagulant therapy) after entry on study may remain on the study without the requirement for further tissue biopsies; this stipulation only applies to the 12 patients enrolled in Cohort II at MTD; the stipulation for provision of biologic specimens, as noted above, excludes the optional pharmacogenomic specimen

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4
  • Uncontrolled infection
  • Any of the following prior therapies:

    • Chemotherapy =< 4 weeks prior to study entry
    • Mitomycin C/nitrosoureas =< 6 weeks prior to study entry
    • Immunotherapy =< 4 weeks prior to study entry
    • Biologic therapy =< 4 weeks prior to study entry
    • Hormonal cancer therapy =< 4 weeks prior to study entry
    • Radiation therapy =< 4 weeks prior to study entry
    • Radiation to > 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Patients on enzyme-inducing anticonvulsants (Phenobarbital, Dilantin, or Tegretol)
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms plus spermicidal agents, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Prior treatment with EGFR targeting therapies (e.g., ZD-1869, EKB-569, OSI-774, CI-1033, GW572016, C225, EMD72000) or Farnesyl transferase inhibitors (R115777, SCH66336, BMS2146632)
  • Major surgery, or significant traumatic injury occurring =< 21 days prior to study entry
  • Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjögren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Gastrointestinal tract disease resulting in an inability to take oral or nasogastric medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy
  • Known brain metastases unless treated with surgery and/or radiation and stable for >= 8 weeks; patient should not be on enzyme-inducing anticonvulsants (Phenobarbital, Phenytoin (Dilantin) or Carbamazepine (Tegretol))
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085553

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Julian Molina Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085553     History of Changes
Other Study ID Numbers: NCI-2012-02597, NCI-2012-02597, CDR0000370818, NCI-6014, MAYO-MC0212, MC0212, 6014, U01CA069912, P30CA015083
Study First Received: June 10, 2004
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 28, 2014