- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00759928
PK Trial of Sorafenib & Erlotinib in Patients With Refractory Solid Tumors
July 1, 2014 updated by: SCRI Development Innovations, LLC
Pharmacokinetic Trial of Sorafenib and Erlotinib in Patients With Refractory Solid Tumors
Two cohorts of patients will be enrolled: Cohort A will consist of patients who are current smokers, and Cohort B will consist of patients who are current nonsmokers.
There will be 24 patients enrolled in each cohort.
Nonsmokers are patients who have not consumed tobacco or nicotine-containing products for 1 year before the start of the study.
Patients classified as current smokers must have smoked a minimum of 10 cigarettes per day for up to 1 year.
Patients who have smoked 1-9 cigarettes per day for up to 1 year, or more than 10 cigarettes per day for less than 1 year will not be eligible for this study.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Compared with supportive care alone, erlotinib has been associated with improved overall survival in patients with Refractory Solid Tumors; however, this absolute benefit is limited for the majority of patients.
Incorporating other biologic agents into the second- or third-line treatment setting may prove to be a successful strategy in improving treatment efficacy (which has been recently demonstrated in several tumor types).
Additionally, recent data suggest that smoking may influence the pharmacokinetic (PK) profile of erlotinib by increasing the metabolic clearance.
Data suggest that the geometric mean erlotinib AUC(0-inf) and C(24h) are significantly decreased in smokers compared with nonsmokers (Hamilton et al. 2006).
For this reason, this trial will enroll separate cohorts of patients who are current smokers and patients who are nonsmokers.
Nonsmokers are patients who have not consumed tobacco or nicotine-containing products for 1 year before the start of the study.
Patients classified as current smokers must have smoked a minimum of 10 cigarettes per day for up to 1 year.
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Fort Myers, Florida, United States, 33916
- Florida Cancer Specialists
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Tennessee
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Nashville, Tennessee, United States, 37203
- Tennessee Oncology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
- Histologically confirmed incurable solid tumors refractory to standard treatment or for which there is no known standard treatment.
- Two cohorts of patients will be enrolled: Cohort A will consist of patients who are current smokers, and Cohort B will consist of patients who are current nonsmokers. Nonsmokers are patients who have not consumed tobacco or nicotine-containing products for 1 year before the start of the study. Patients classified as current smokers must have smoked a minimum of 10 cigarettes per day for <1 year.
- Patients must have evaluable disease.
- Recovery from any toxic effects of prior therapy to grade 1 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
- Completion of radiation therapy at least 21 days prior to the start of study treatment (not including palliative local radiation).
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Absolute neutrophil count (ANC) >1,500/mL and platelets >75,000/mL (within 7 days prior to study treatment).
- Hemoglobin >9 g/dL (within 7 days prior to treatment). Patients may be transfused or receive erythropoietin to maintain or exceed this level where otherwise indicated.
- International normalized ratio (INR) <1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution (if patient is not on anti-coagulation therapy; patients receiving anticoagulation treatment with an agent such as warfarin or heparin may be allowed to participate with the therapeutic range established prior to the initiation of study treatment).
- Serum creatinine <1.5 x the institutional upper limit of normal (ULN) within 7 days prior to study treatment. If the absolute value is greater than 2 mg/dL, the creatinine clearance (calculated according to the Cockcroft-Gault formula) must be > 45 mL/min for the patient to be eligible for the study.
- Transaminases <3 x the institutional ULN (except if there is known hepatic metastasis, wherein transaminases may be <5 x institutional ULN).
- Total bilirubin <1.5 times ULN.
- Patients must be able to understand the nature of this study, give written informed consent, and comply with study requirements.
- Agreement of female patients of childbearing potential and male patients who have partners of childbearing potential to use an effective form of contraception to prevent pregnancy during treatment, and for a minimum of 90 days thereafter. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
Exclusion
- Patients with untreated brain metastases. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis. Patients who have a history of brain metastases that has been treated by surgery or radiation therapy > 4 weeks with no signs of Central Nervous System (CNS) progression are allowed.
- Women who are pregnant or lactating.
- Patients whose last dose of chemotherapy, immunotherapy, or investigational drug therapy was completed < 21 days prior to receiving study drug
Significant cardiac disease within 90 days of starting study treatment including:
- superior vena cava syndrome;
- new onset angina;
- congestive heart failure (CHF) > Class 2 per New York Heart Association (NYHA) classification (see Appendix B);
- ventricular arrhythmia;
- valvular heart disease.
- Myocardial infarction (MI) within 6 months prior to initiation of study treatment.
- Cardiomegaly on chest imaging or CHF > Class 2 per NYHA classification (see Appendix B) unless the left ventricular ejection fraction (LVEF) is within normal range for the institution within 3 months of initiating therapy.
- Poorly controlled hypertension (defined as systolic blood pressure [BP] >150 mmHg and/or diastolic blood pressure >90 mmHg on anti-hypertensive medications).
- Unstable angina (anginal symptoms at rest).
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
- A serious active infection (> grade 2) at the time of treatment
- A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
- A major surgical procedure within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
- Any minor surgery must be completed within 7 days prior to beginning study treatment.
- Use of rifampin, St. John's wort, or other potent inducers of CYP3A4 are not permitted from Day -14 through Day 15 of the study (see Appendix C).
- Use of ketoconazole and other potent inhibitors of CYP3A4 are not permitted from Day -14 through Day 15 of the study (see Appendix C).
- Stroke or transient ischemic attack (TIA) within the past 6 months.
- Any prior history of hypertensive crisis or hypertensive encephalopathy.
- Pulmonary hemorrhage/bleeding event > grade 2 within 28 days of study treatment.
- Any other non-pulmonary hemorrhage/bleeding event> grade 3 within 28 days of study treatment.
- Evidence or history of bleeding diathesis or coagulopathy.
- Serious non-healing wound, ulcer, or bone fracture.
- Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
- Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease.
- Patients who smoke 1-9 cigarettes per day during the year before study entry or patients who have smoked for <1 year will not be eligible for this study.
- Any condition that impairs the patient's ability to swallow whole pills.
- Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Erlotinib/Sorafenib
Patients will receive erlotinib 150 mg once daily by mouth and sorafenib 400 mg twice daily by mouth.
The study will begin with a 2-week run-in period (which will begin on Day 14 of the study, and continue through Day 1 of the study), in which erlotinib will be dosed alone at 150 mg once daily.
Patients will continue taking erlotinib as a single agent at 150 mg once daily through Day 1.
After the 2-week run-in period, patients will receive continuous dosing of both agents (erlotinib 150 mg once daily and sorafenib 400 mg twice daily) in cycles of 28 days each.
Toxicity will be assessed every cycle (every 4 weeks) for all patients.
Because this is not an efficacy study, restaging tumor measurements will be at the discretion of the physician every 8 weeks during treatment.
Patients with objective response or stable disease will continue therapy; patients with disease progression or unacceptable toxicity will be discontinued from the study.
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150 mg once daily by mouth
Other Names:
400 mg twice daily by mouth
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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To determine the pharmacokinetics (PK) of erlotinib when administered in combination with sorafenib on a continuous schedule in Refractory Solid Tumors in patients who are smokers and in patients who are nonsmokers.
Time Frame: 3 months
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3 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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To evaluate safety of this combination in patients with Refractory Solid Tumors.
Time Frame: 3 months
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3 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Chair: David R. Spigel, M.D., SCRI Development Innovations, LLC
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2008
Primary Completion (Actual)
September 1, 2013
Study Completion (Actual)
June 1, 2014
Study Registration Dates
First Submitted
September 24, 2008
First Submitted That Met QC Criteria
September 24, 2008
First Posted (Estimate)
September 25, 2008
Study Record Updates
Last Update Posted (Estimate)
July 2, 2014
Last Update Submitted That Met QC Criteria
July 1, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SCRI LUN 175
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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