A MULTICENTER, RANDOMIZED, DOUBLE BLIND, CONTROLLED PHASE 3, EFFICACY AND SAFETY STUDY OF SUNITINIB (SU011248) IN PATIENTS WITH ADVANCED/METASTATIC NON SMALL CELL LUNG CANCER TREATED WITH ERLOTINIB

Phase 1

• Conditions: ocally advanced or metastatic non small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen.; MedDRA version: 9.1 Level: LLT Classification code 10059515 Term: Non-small cell lung cancer metastatic

• Registration Number: EUCTR2007-001915-52-GB
• Lead Sponsor: Pfizer Inc., 235 East 42nd Street, New York, 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-06-03
• Study Completion: 2012-12-20
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 956

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Histologically or cytologically proven diagnosis of NSCLC with evidence of disease that is recurrent (after treatment for Stage IIIB with malignant effusion or Stage IV NSCLC) and for which erlotinib treatment is clinically indicated. Note: Diagnosis via sputum is not considered acceptable.
2. Prior treatment with 1 or 2 chemotherapy regimens (must have included a platinum-based regimen) for advanced disease (Stage IIIB with malignant effusion or Stage IV NSCLC).
3. Disease progression during or after first-line chemotherapy
4. Measurable or nonmeasurable disease.
5. Male or female, 18 years of age or older.
6. ECOG performance status 0 or 1.
7. Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade =1 (except alopecia).
8. Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =2.5 x
upper limit of normal (ULN), or AST and ALT =5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin =1.5 x ULN
• Serum albumin =3.0 g/dL
• Absolute neutrophil count (ANC) =1500/µL
• Platelets =100,000/µL
• Hemoglobin =9.0 g/dL
• Serum creatinine =1.5 x ULN
9. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects presenting with any of the following will not be included in the trial:
1. Prior treatment with any receptor tyrosine kinase inhibitors (including but not limited to sunitinib, erlotinib, and gefitinib), VEGF inhibitors (with the exception of bevacizumab), or other angiogenesis inhibitors (including but not limited to thalidomide). Note: Patients previously treated with cetuximab will not be considered eligible for study entry.
2. Treatment with sunitinib and/or erlotinib if it is contraindicated according to the local prescribing information.
3. Major surgery within 4 weeks of study treatment. At least 7 days should elapse since minor surgical procedure including placement of an access device or fine needle aspiration.
4. Tumor (any histology) that involves a major blood vessel (eg, no aortic involvement).
5. Major radiation therapy within 4 weeks of study treatment except palliative radiotherapy to non-target metastatic lesions.
6. Systemic anticancer therapy within 4 weeks of starting the study treatment.
7. Prior treatment with a platinum-based regimen as adjuvant therapy following resection for early-stage NSCLC.
8. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
9. Prior radiation therapy to >25% of the bone marrow.
10. Evidence of hemoptysis <4 weeks of starting study treatment. Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24 hour period in the best estimate of the Investigator.
11. Presence or history of brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
12. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of the cervix uteri.
13. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolism.
14. Ongoing cardiac dysrhythmias of NCI CTCAE grade =2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females.
15. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
16. Severe dry eye syndrome, Sjogren's syndrome, severe exposure keratopathy, bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis, or clinically
significant gastrointestinal abnormalities including uncontrolled inflammatory disease
(eg, Crohn's or ulcerative colitis).
17. Known human immunodeficiency virus infection.
18. Current treatment on another clinical trial.
19. Pregnancy or breastfeeding. Female, who is pregnant or nursing; fertile patient who is unwilling or unable to use adequate contraception to prevent pregnancy during the program (Section 4.3). All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study entry.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: Primary Objective:<br> • To demonstrate that the combination of sunitinib plus erlotinib is superior to erlotinib plus placebo in prolonging the overall survival for advanced/metastatic NSCLC patients who have received 1 to 2 prior chemotherapy regimens.<br> ;<br> Secondary Objective: Secondary Objectives:<br> • To compare measures of antitumor response [progression-free survival (PFS); overall response rate (ORR)] between both treatment arms and estimate duration of tumor control [duration of response (DR)].<br> • To compare the safety and tolerability of erlotinib plus sunitinib versus erlotinib plus<br> placebo in this patient population<br> • To assess patient-reported outcomes.<br> ;Primary end point(s): Overall Survival (OS)