Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer
Condition: Recurrent Non-Small Cell Lung Carcinoma; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Laboratory Biomarker Analysis; Pemetrexed Disodium; Sunitinib Malate
Intervention description: Correlative studies; Given IV; Given PO
Intervention MeSH terms: Pemetrexed; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 130.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies pemetrexed disodium and sunitinib malate to compare
      how well they work when given alone or together as second-line therapy in treating patients
      with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as
      pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow
      to the tumor. It is not yet known whether pemetrexed disodium and sunitinib malate are more
      effective when given alone or together in treating non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic documentation: histologic or cytologic documentation of NSCLC

          -  Stage: IIIB/IV with evidence of disease progression following first-line therapy

          -  Tumor site: lung (non-small cell)

          -  No cavitary lesions

          -  Only one prior chemotherapy regimen in the first-line stage IIIB/IV setting is
             allowed; this could have been either a platinum- or non-platinum-based regimen

          -  First-line therapy must be completed >= 28 days before registration

          -  Prior adjuvant therapy is allowed provided the patient had one previous regimen in the
             advanced stage IIIB/IV setting

          -  At least 28 days from prior major surgery and at least 14 days from any prior
             radiotherapy before registration

          -  No prior inhibitors of VEGF receptor (VEGFR) (e.g., SU5416, SU6668, AZ6474, SU11248,
             PTK787, AZD2171, AEE-788, sorafenib); prior treatment with epidermal growth factor
             receptor (EGFR) inhibitors and bevacizumab is allowed, provided at least 4 weeks has
             elapsed

          -  No prior pemetrexed

          -  Patients must have measurable or non-measurable disease

               -  Measurable disease

                    -  Lesions that can be accurately measured in at least one dimension (longest
                       diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1
                       cm with spiral computed tomography (CT) scan

               -  Non-measurable disease

                    -  All other lesions, including small lesions (longest diameter < 20 mm with
                       conventional techniques or < 10 mm with spiral CT scan) and truly
                       nonmeasurable lesions

               -  Lesions that are considered non-measurable include the following:

                    -  Bone lesions

                    -  Leptomeningeal disease

                    -  Ascites

                    -  Pleural/pericardial effusion

                    -  Lymphangitis cutis/pulmonis

                    -  Abdominal masses that are not confirmed and followed by imaging techniques

                    -  Cystic lesions

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Pregnant or nursing mothers are not eligible for this study; patients in their child
             bearing years must have a baseline negative pregnancy test (in the case of females);
             males and females must practice appropriate contraceptive measures during the period
             of protocol therapy and for 6 months after completion of protocol therapy; appropriate
             methods of birth control include abstinence, oral contraceptives, implantable hormonal
             contraceptives (Norplant), or double barrier method (diaphragm plus condom)

          -  No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT
             interval (QTc interval) > 500 msec (within 2 years prior to registration); the use of
             agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide,
             sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, flecainide) is not
             recommended while on protocol therapy

          -  Patients with class I New York Heart Association (NYHA) heart failure are eligible;
             patients with a history of class II NYHA heart failure are eligible, provided they
             meet at least one of the following criteria:

               -  Patients with a history of class II heart failure who are asymptomatic on
                  treatment

               -  Patients with prior anthracycline exposure

               -  Patients who have received central thoracic radiation that included the heart in
                  the radiotherapy port

          -  Patients with a history of symptomatic congestive heart failure within 12 months prior
             to entry are not eligible

          -  No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft or stenting, cerebrovascular accident or transient ischemic attack within the
             last year

          -  Patients with hypertension that cannot be controlled by medications (> 150/100 mmHg
             despite optimal medical therapy) are not eligible

          -  Patients who require use of therapeutic anticoagulation for thromboembolic disease are
             not eligible; Note: low doses of Coumadin (up to 2 mg daily) are permitted for
             prophylaxis of thrombosis

          -  No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome

          -  No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis;
             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

          -  Patients with a history of hypothyroidism or hyperthyroidism are eligible, provided
             they are currently euthyroid

          -  None of the following within 28 days of beginning treatment: abdominal fistula,
             gastrointestinal perforation, intra-abdominal abscess, serious or non-healing wound,
             ulcer, or bone fracture

          -  The use of the following specific inhibitors and inducers of cytochrome P450, family
             3, subfamily A, polypeptide 4 (CYP3A4) is not permitted; the following inhibitors of
             CYP3A4 are prohibited within 7 days before and during treatment with sunitinib: azole
             antifungals (ketoconazole, itraconazole), diltiazem, clarithromycin, erythromycin,
             verapamil, delavirdine, and human immunodeficiency virus (HIV) protease inhibitors
             (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); the following inducers of
             CYP3A4 are prohibited within 12 days before beginning and during treatment with
             sunitinib: rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's
             Wort, efavirenz, tipranavir

               -  Other inhibitors and inducers of CYP3A4 may be used if necessary, but their use
                  is discouraged

          -  No symptomatic or untreated central nervous system (CNS) metastases; patients with CNS
             metastases must be asymptomatic, must have received definitive therapy (>= 6 weeks
             since resection or >= 2 weeks since radiotherapy) for brain metastases, and be off
             steroids or on a stable dose for 2 weeks prior to registration

          -  No chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal
             antiinflammatory agents known to inhibit platelet function; treatment with
             dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or
             cilostazol (Pletal) is not allowed

          -  No pleural effusions or ascites that are detectable on physical exam