PK Trial of Sorafenib & Erlotinib in Patients With Refractory Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00759928
First received: September 24, 2008
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Refractory Solid Tumors
Drug: Erlotinib
Drug: Sorafenib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic Trial of Sorafenib and Erlotinib in Patients With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate safety of this combination in patients with Refractory Solid Tumors. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: October 2008
Study Completion Date: June 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Erlotinib
150 mg once daily by mouth
Other Name: Tarceva
Drug: Sorafenib
400 mg twice daily by mouth
Other Name: Nexavar

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Histologically confirmed incurable solid tumors refractory to standard treatment or for which there is no known standard treatment.
  2. 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.
  3. Patients must have evaluable disease.
  4. 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.
  5. Completion of radiation therapy at least 21 days prior to the start of study treatment (not including palliative local radiation).
  6. An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  7. Absolute neutrophil count (ANC) >1,500/mL and platelets >75,000/mL (within 7 days prior to study treatment).
  8. 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.
  9. 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).
  10. 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.
  11. Transaminases <3 x the institutional ULN (except if there is known hepatic metastasis, wherein transaminases may be <5 x institutional ULN).
  12. Total bilirubin <1.5 times ULN.
  13. Patients must be able to understand the nature of this study, give written informed consent, and comply with study requirements.
  14. 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

  1. 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.
  2. Women who are pregnant or lactating.
  3. Patients whose last dose of chemotherapy, immunotherapy, or investigational drug therapy was completed < 21 days prior to receiving study drug
  4. 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.
  5. Myocardial infarction (MI) within 6 months prior to initiation of study treatment.
  6. 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.
  7. Poorly controlled hypertension (defined as systolic blood pressure [BP] >150 mmHg and/or diastolic blood pressure >90 mmHg on anti-hypertensive medications).
  8. Unstable angina (anginal symptoms at rest).
  9. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  10. Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
  11. A serious active infection (> grade 2) at the time of treatment
  12. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  13. A major surgical procedure within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
  14. Any minor surgery must be completed within 7 days prior to beginning study treatment.
  15. 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).
  16. Use of ketoconazole and other potent inhibitors of CYP3A4 are not permitted from Day -14 through Day 15 of the study (see Appendix C).
  17. Stroke or transient ischemic attack (TIA) within the past 6 months.
  18. Any prior history of hypertensive crisis or hypertensive encephalopathy.
  19. Pulmonary hemorrhage/bleeding event > grade 2 within 28 days of study treatment.
  20. Any other non-pulmonary hemorrhage/bleeding event> grade 3 within 28 days of study treatment.
  21. Evidence or history of bleeding diathesis or coagulopathy.
  22. Serious non-healing wound, ulcer, or bone fracture.
  23. Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
  24. 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.
  25. 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.
  26. Any condition that impairs the patient's ability to swallow whole pills.
  27. Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00759928

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33916
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bayer
Investigators
Study Chair: David R. Spigel, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00759928     History of Changes
Other Study ID Numbers: SCRI LUN 175
Study First Received: September 24, 2008
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Refractory Solid Tumors
Unresectable Stage III/IV
Sorafenib
Erlotinib
Pharmacokinetics

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

ClinicalTrials.gov processed this record on August 01, 2014