Expired Study
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Rochester, Minnesota 55905


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.


Study summary:

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.


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 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 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))


Study is Available At:


Original ID:

NCI-2012-02597


NCT ID:

NCT00085553


Secondary ID:

NCI-2012-02597


Study Acronym:


Brief Title:

Tipifarnib and Erlotinib Hydrochloride in Treating Patients With Advanced Solid Tumors


Official Title:

Phase I Trial of R115777 and OSI-774 in Patients With Advanced Solid Tumors


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

29


Enrollment Type:

Actual


Overall Contact Information

Official Name:Julian Molina
Principal Investigator
Mayo Clinic

Study Dates

Start Date:May 20, 2004
Completion Date:May 16, 2018
Completion Type:Actual
Primary Completion Date:May 7, 2008
Primary Completion Type:Actual
Verification Date:May 2018
Last Changed Date:May 17, 2018
First Received Date:June 10, 2004

Study Outcomes

Outcome Type:Primary Outcome
Measure:Incidence of all adverse events, graded according to the National Cancer Institute Common (NCI) Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame:Up to 30 days after last study treatment
Safety Issues:False
Description: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.
Outcome Type:Primary Outcome
Measure:Incidence of toxicity graded according to NCI CTCAE version 3.0
Time Frame:Up to 3 months
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Description:Best Response is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Responses
Outcome Type:Secondary Outcome
Measure:Time until any treatment related toxicity
Time Frame:Up to 30 days after last study treatment
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Time until treatment related grade 3+ toxicity
Time Frame:Up to 30 days after last study treatment
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Time until hematologic nadirs (white blood cells, ANC, platelets)
Time Frame:Up to 3 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Time to progression
Time Frame:Up to 3 months
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Time to treatment failure
Time Frame:Time from registration to documentation of progression, unacceptable toxicity, or refusal to continu
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Erlotinib Hydrochloride
Description:Given PO
Arm Name:Treatment (erlotinib hydrochloride, tipifarnib)
Other Name:Cp-358,774
Intervention Type:Other
Name:Laboratory Biomarker Analysis
Description:Correlative studies
Arm Name:Treatment (erlotinib hydrochloride, tipifarnib)
Intervention Type:Other
Name:Pharmacological Study
Description:Correlative studies
Arm Name:Treatment (erlotinib hydrochloride, tipifarnib)
Intervention Type:Drug
Name:Tipifarnib
Description:Given PO
Arm Name:Treatment (erlotinib hydrochloride, tipifarnib)
Other Name:R115777

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (erlotinib hydrochloride, tipifarnib)
Description: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)

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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