Clinical trial NCT00609804: Sorafenib and Erlotinib or Sorafenib Alone in Advanced Non-Small Cell Lung Cancer Progressing on Erlotinib
Official title: Randomized Phase II Trial of Sorafenib and Erlotinib or Sorafenib Alone in Patients With Advanced Non-Small Cell Lung Cancer Progressing on Erlotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Advanced
Erlotinib
Sorafenib
Progressing on erlotinib
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Bayer
name: OSI Pharmaceuticals
First posted: 2008-02-07
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, multi-center, Phase II study of treatment of patients with advanced NSCLC who have progressed on erlotinib with the combination of sorafenib and erlotinib or sorafenib alone.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed stage IIIB/IV or relapsed non-small cell lung carcinoma (squamous carcinoma, adenocarcinoma, or large cell carcinoma). Patients with mixed tumors with small-cell elements are ineligible.
2. Patients with no more than 2 prior lines of therapy, with the latest of those therapies being single-agent erlotinib.
3. Evidence of progressive disease on erlotinib as assessed by the treating physician. Erlotinib must be the last treatment for NSCLC prior to enrollment into this study. Patients may be on erlotinib until enrollment. If erlotinib has already been stopped, the period of time off Erlotinib cannot exceed 14 days prior to study enrollment.
4. Patients must have experienced a clinical benefit (complete response \[CR\], partial response \[PR\], or stable disease \[SD\]) from prior therapy with erlotinib for a period of 8 weeks.
5. Patient must have one measurable lesion measuring at least 10 mm in the longest diameter (LD) by spiral computed tomography (CT), or 20 mm with conventional techniques according to the Response Evaluation Criteria in Solid Tumors (RECIST).
6. Recovery from any toxic effects of erlotinib to ≤ grade 1 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
7. Completion of palliative radiation therapy prior to the start of study treatment. Previously irradiated lesions in the advanced setting cannot be included as target lesions unless clear tumor progression has been observed following the completion of radiation therapy.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
9. Absolute neutrophil count (ANC) \>=1,500 and platelets \>=75,000 (within 7 days prior to initial study treatment).
10. Hemoglobin \>=9 g/dL (within 7 days prior to initial treatment).
11. International normalized ratio (INR) \<=1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution if not on anticoagulation therapy. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate with the therapeutic range established prior to study treatment initiation.
12. Serum creatinine \<=1.5 x institutional upper limit of normal (ULN) within 7 days prior to initial study treatment. If the absolute value is greater than 2mg/dL, the creatinine clearance, calculated according to the Cockroft-Gault formula, must be \>=45 mL/min to be eligible.
13. Bilirubin \<=1.5 x the ULN; transaminases \<=3 x institutional ULN, except in known hepatic metastasis, wherein these may be \>=5 x institutional ULN.
14. Patients must be able to understand the nature of this study, give written informed consent, and comply with study requirements.
15. Agreement of male patients (with partners of childbearing potential) and female patients of childbearing potential to use effective contraception to prevent pregnancy during treatment and for a minimum of 90 days thereafter. Additionally, women should not breastfeed during this time.

Exclusion Criteria:

1. Past or current history of neoplasm other than the entry diagnosis, with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone, and a disease-free survival (DFS) \>=3 years.
2. Pregnancy or lactation. All females of child-bearing potential must have negative serum or urine pregnancy tests within 7 days prior to study treatment.
3. Prior epithelial growth factor receptor (EGFR) inhibitors, with the exception of erlotinib, are not allowed. This includes both tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. Prior vascular endothelial growth factor (VEGF) inhibitors, with the exception of bevacizumab, are not allowed.
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
   * arrhythmia
   * valvular heart disease.
5. Myocardial infarction within 6 months prior to initiation of study treatment
6. Cardiomegaly on chest imaging or ventricular hypertrophy on electrocardiogram (ECG) unless the left ventricular ejection fraction (LVEF) is within normal range for the institution.
7. Poorly controlled hypertension (defined as systolic blood pressure \[BP\] \>150 mm Hg and/or diastolic BP \>100 mm Hg on antihypertensive 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. Untreated brain metastases. Patients who have treated metastases \>=4 weeks out (with surgery and/or radiation therapy) and no evidence of central nervous system (CNS) progression are eligible.
14. Treatment with a non-approved or investigational drug within 28 days of initial study treatment.
15. A major surgical procedure, open biopsy, or significant traumatic injury within 28 days of beginning treatment or anticipation of need for major surgery during the course of the study.
16. Thrombolic or embolic events such as a stroke and transient ischemic attack (TIA) within the past 6 months.
17. Any prior history of hypertensive crisis or hypertensive encephalopathy.
18. Pulmonary hemorrhage/bleeding event \>= grade 2 within 28 days of initial study treatment.
19. Any other non-pulmonary hemorrhage/bleeding event \>= grade 3 within 28 days of initial study treatment.
20. Evidence or history of bleeding diathesis or coagulopathy.
21. Serious non-healing wound, ulcer, or bone fracture.
22. Use of St. John's Wort or rifampin (rifampicin).
23. Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
24. Any malabsorption problem.
25. Any condition that impairs the patient's ability to swallow whole pills.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 18 months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 18 months
measure: Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Cancer Research
state: Georgia
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic, LLP
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Bethesda
country: United States
facility: National Capital Clinical Research Consortium
state: Maryland
city: Jackson
country: United States
facility: Jackson Oncology Associates
state: Mississippi
city: Chesterfield
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Cancer Center
state: Nebraska
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ
state: New Jersey
city: Chattanooga
country: United States
facility: Associates in Hematology Oncology
state: Tennessee
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David Spigel, M.D.
role: STUDY_CHAIR
References:
citation: Spigel DR, Rubin MS, Gian VG, Shipley DL, Burris HA 3rd, Kosloff RA, Shih KC, Quinn R, Greco FA, Hainsworth JD. Sorafenib and continued erlotinib or sorafenib alone in patients with advanced non-small cell lung cancer progressing on erlotinib: A randomized phase II study of the Sarah Cannon Research Institute (SCRI). Lung Cancer. 2017 Nov;113:79-84. doi: 10.1016/j.lungcan.2017.09.007. Epub 2017 Sep 18.