Randomzied Phase 2 Trial of AG-013736 or Bevacizumab in Combination with Paclitaxel and Carboplatin as First Line Treatment For Patients with Advanced Non-small Cell Lung Cancer

• Conditions: First line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC); MedDRA version: 9.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastatic; MedDRA version: 9.1Level: LLTClassification code 10029515Term: Non-small cell lung cancer recurrent; MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IV

• Registration Number: EUCTR2007-006682-33-GB
• Lead Sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-12-28
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

1. Histologically- or cytologically-confirmed diagnosis of advanced non-squamous cell,
NSCLC with documented Stage IIIB with pleural effusion, or Stage IV or recurrent
disease.
2. At least one site of measurable disease (per RECIST). Measurable disease that has been previously irradiated will not be considered a target lesion unless the lesion diameter has grown by =20 % since completion of the prior radiation therapy or if the lesion is a new lesion, assuming all other criteria are met.
3. No prior systemic treatment for NSCLC except prior adjuvant/neo-adjuvant therapy if last dose was >12 months prior to enrollment.
4. Adequate organ function as determined by the following criteria:
• Absolute neutrophil count (ANC) =1500 cells/mm3;
• Platelet count =100,000 cells/mm3;
• Hemoglobin =9 g/dL;
• Serum creatinine =1.5 x upper limit of normal (ULN) or calculated creatinine clearance =60 mL/min;
• 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;
• Urine protein:creatinine ratio <0.5.
5. Age =18 years.
6. ECOG performance status of 0 or 1.
7. Life expectancy >12 weeks.
8. Prior surgery or radiation therapy is permitted. Radiation therapy must have completed
=21 days 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 (if necessary) must have been completed =7 days prior to treatment.
9. Female patients may not be pregnant or breastfeeding. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 6 months thereafter.
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of patient reported outcome measures.
11. 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

1. Histologic evidence of predominantly squamous-cell NSCLC.
2. Prior treatment with systemic therapy for advanced disease.
3. Prior treatment with a VEGF or VEGFR inhibitor.
4. 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.
5. Known central nervous system (CNS) metastasis. CNS imaging at baseline is required.
6. Current or recent (within 1 month) use of a thrombolytic agent.
7. History of a hematologic diathesis or coagulopathy within 6 months of study entry
8. Need for therapeutic anticoagulation (at time of screening).
9. Ongoing or recent (within 10 days prior to treatment start) need for full therapeutic dose of oral or parenteral anticoagulant or chronic daily treatment with aspirin (>325 mg/day)
or clopidogrel (>75 mg/day).
10. History of hemoptysis =½ tsp of bright red blood per day within 4 weeks of enrollment.
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 surgical procedures affecting absorption including 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 without evidence of resolution documented by endoscopy or colonoscopy;
• Malabsorption syndromes.
13. Active, invasive malignancies other than NSCLC:
• The patient may not have radiographic or clinical signs of another cancer, and must
not be getting any form of treatment for cancer.
14. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, itraconazole, erythromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine) is not permitted.
15. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John’s wort) is not permitted. (Note: The short-term use of dexamethasone as a premedication for chemotherapy is not an exclusion criterion).
16. Acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study.

Study & Design

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