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Pharmacokinetic Trial of Sorafenib and Erlotinib in Patients With Refractory Solid Tumors


N/A
18 Years
N/A
Open (Enrolling)
Both
Refractory Solid Tumors

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Trial Information

Pharmacokinetic Trial of Sorafenib and Erlotinib in Patients With Refractory Solid Tumors


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 ≥1 year.

Inclusion 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 Cockroft-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 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

3 months

Safety Issue:

No

Authority:

United States: Food and Drug Administration

Study ID:

SCRI LUN 175

NCT ID:

NCT00759928

Start Date:

October 2008

Completion Date:

December 2012

Related Keywords:

  • Refractory Solid Tumors
  • Refractory Solid Tumors
  • Unresectable Stage III/IV
  • Sorafenib
  • Erlotinib
  • Pharmacokinetics
  • Neoplasms

Name

Location

Tennessee OncologyNashville, Tennessee  37203