RANDOMIZED PHASE 2 STUDY OF CISPLATIN/PEMETREXED WITH OR WITHOUT AXITINIB (AG-013736) AS FIRST-LINE TREATMENT FOR PATIENTS WITH NON-SQUAMOUS NON-SMALL CELL LUNG CANCER - ND

Conditions: patients with locally advanced, recurrent, or metastatic non-squamous, non-small cell lung cancer (NSCLC).
MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB

Registration Number: EUCTR2008-004009-32-IT

Lead Sponsor: PFIZER

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 160

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Histologically- or cytologically confirmed diagnosis of adenocarcinoma, large cell or bronchioloalveolar non-small cell lung cancer. Cytologic specimens for diagnosis or for cell type classification must have been obtained from bronchial brushings or washings or from needle aspiration of a defined lesion. Sputum cytology alone will not be acceptable for diagnosis or for cell type classification. Patients with mixed NSCLC with predominantly squamous cell carcinoma should be classified as squamous and thus do not qualify for this study. 2. Stage IIIB with malignant effusion (with cytologic confirmation of malignant pleural or pericardial effusion), Stage IV, or recurrent disease after definitive loco-regional therapy. 3. Candidate for primary treatment with cisplatin and pemetrexed 4. At least one measurable target lesion per RECIST. Previously irradiated measurable lesion may not be considered a target lesion unless a progression is documented at the site after the completion of radiation therapy. 5. Adequate organ function as defined by the following criteria: Absolute neutrophil count (ANC) ≥1500 cells/mm3 Platelet count ≥100,000 cells/mm3 01000007818217 \ Hemoglobin ≥9 g/dL AST and ALT <2.5 x ULN, or AST and ALT <5 x ULN if liver function abnormalities are due to underlying malignancy Total bilirubin ≤1.5 x ULN Calculated creatinine clearance or measured creatinine clearance ≥60 mL/min. . Urine protein <1+ by dipstick. If dipstick is ≥1+, then urine protein:creatinine ratio must be <1 to be eligible. 6. Age ≥18 years 7. Life expectancy >12 weeks 8. ECOG performance status of 0 or 1 9. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible. 10. Women of child-bearing potential must have a negative serum or urine pregnancy test ≤3 days prior to starting treatment and may not be breast feeding. 11. Fertile patients or their partners must be surgically sterile, be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. 12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcomes. 13. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment.
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 exclusion criteria are not eligible for enrollment into the study: 1. Any histological/cytological evidence of predominantly squamous NSCLC. Small cell or carcinoid lung cancer patients are also ineligible. 01000007818217 \large cell or bronchioloalveolar). 3. Prior systemic therapy for Stage IIIB (with malignant effusion), Stage IV, or recurrent NSCLC. (Prior treatment with systemic therapy as adjuvant chemotherapy or in conjunction with radiotherapy for Stage II or III NSCLC is permitted if the last dose of chemotherapy was completed 12 months or more prior to randomization). 4. Prior treatment with a VEGF or VEGFR inhibitor. 5. One or more lung lesions with cavitation, or any lesion invading or abutting a major blood vessel (as assessed by CT and/or MRI). 6. History of hemoptysis > œ teaspoon (2.5 ml) of blood in any 24-hour period within prior 2 weeks of enrollment. 7. NCI CTCAE Grade 3 hemorrhage from any cause <4 weeks before enrollment. 8. Radiation therapy completed < 28 days (unless the radiation was limited to skeletal lesions) prior to start of treatment or major surgery < 28 days prior to start of treatment. All acute toxicities must have resolved to baseline or to CTC Grade 1 (NCI CTCAE v3.0). Fine needle aspiration procedures or minor surgeries must have been completed at least 7 days prior to treatment. 9. Untreated brain metastases. Patients with previously diagnosed CNS metastases are eligible if they have completed radiation therapy to the CNS at least 4 weeks prior to randomization, have recovered from the acute effects of that treatment before enrollment, have discontinued corticosteroid treatment for at least 2 weeks, have not taken potent anticonvulsants that are CYP3A4 inducers for at least 2 weeks, and are neurologically stable. 10. Need for therapeutic anticoagulation, regular use of aspirin (> 325 mg/day), NSAID or other medications known to inhibit platelet function. (Low-dose anticoagulants, such as low-dose heparin or 1-2 mg/day of coumadin for prevention of deep venous thrombosis or maintenance of patency of central venous access devices is permitted). 11. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism. 12. Gastrointestinal abnormalities including: inability to take oral medication; requirement for intravenous alimentation; prior total gastric resection; treatment for active peptic ulcer disease in the past 6 months; active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia, or melena in the past 3 months; malabsorption syndromes.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess efficacy of axitinib given continuously in combination with pemetrexed/cisplatin in patients with non-squamous NSCLC compared to pemetrexed/cisplatin alone. To assess efficacy of axitinib given in a modified schedule in combination with pemetrexed/cisplatin in patients with non-squamous NSCLC compared to pemetrexed/cisplatin alone.;Secondary Objective: To assess the safety of axitinib in combination with pemetrexed/cisplatin in patients with non-squamous NSCLC. To explore the severity of symptoms and the interference on various aspects of life as noted by patients in each treatment arm.;Primary end point(s): Progression Free Survival (PFS) defined as the time from randomization to the date of progression or death due to any cause, whichever occurs first. 01000007818217 \

Secondary Outcome Measures

Name	Time	Method

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