Tipifarnib and Erlotinib Hydrochloride in Treating Patients With Advanced Solid Tumors

NCT00085553 | Completed Phase 1

• 8 other identifiers: NCI-2012-02597CDR0000370818NCI-6014MAYO-MC0212MC02126014P30CA015083U01CA069912
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of all adverse events, graded according to the National Cancer Institute Common (NCI) Terminology Criteria for Adverse Events (CTCAE) version 3.0

  The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

  Up to 30 days after last study treatment

• Incidence of toxicity graded according to NCI CTCAE version 3.0

  Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  Up to 3 months

Secondary Outcomes (6)

• Best response as assessed by the Response Evaluation Criteria in Solid Tumors

  Start of the treatment until disease progression/recurrence, assessed up to 3 months

• Time until any treatment related toxicity

  Up to 30 days after last study treatment

• Time until treatment related grade 3+ toxicity

  Up to 30 days after last study treatment

• Time until hematologic nadirs (white blood cells, ANC, platelets)

  Up to 3 months

• Time to progression

  Up to 3 months

Other Outcomes (3)

• Inhibition of EGFR from tumor biopsies

  Up to day 21 of course 1

• Inhibition of FT from tumor biopsies

  Up to day 21 of course 1

• Incidence of any genetic polymorphisms

  Up to day 21 of course 1

Study Arms (1)

Treatment (erlotinib hydrochloride, tipifarnib)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Tipifarnib

Interventions

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Treatment (erlotinib hydrochloride, tipifarnib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (erlotinib hydrochloride, tipifarnib)

Pharmacological Study OTHER

Correlative studies

Treatment (erlotinib hydrochloride, tipifarnib)

Tipifarnib DRUG

Given PO

Also known as: R115777, Zarnestra

Treatment (erlotinib hydrochloride, tipifarnib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 x 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Erlotinib Hydrochloride; tipifarnib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Julian Molina

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: May 20, 2004
• Primary Completion: May 7, 2008
• Study Completion: May 16, 2018
• Last Updated: May 18, 2018

Record last verified: 2018-05

Locations

US (1)