Pemetrexed Disodium With or Without Sorafenib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: pemetrexed disodium; sorafenib tosylate
Intervention description: given IV; given orally
Intervention MeSH terms: Pemetrexed; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenosquamous cell lung cancer; adenocarcinoma of the lung

Summary:

      RATIONALE: Pemetrexed disodium and sorafenib may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells
      by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib may
      kill more tumor cells.

      PURPOSE: This randomized phase II trial is studying pemetrexed disodium and sorafenib to see
      how well they work compared with pemetrexed disodium alone as second-line therapy in treating
      patients with stage IIIB or stage IV non-small cell lung cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed non-squamous cell non-small cell lung cancer
             (NSCLC)

               -  Stage IIIB or IV disease

               -  Squamous cell carcinomas are not allowed

                    -  Adenosquamous histology allowed

          -  Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by
             conventional techniques or ≥ 1.0 cm by spiral CT scan

               -  No nonmeasurable disease only, including small lesions and truly nonmeasurable
                  lesions, including any of the following:

                    -  Bone lesions

                    -  Leptomeningeal disease

                    -  Ascites

                    -  Pleural/pericardial effusion

                    -  Inflammatory breast disease

                    -  Lymphangitis cutis/pulmonis

                    -  Abdominal masses that are not confirmed and followed by imaging techniques

                    -  Cystic lesions

          -  Previously treated with 1 chemotherapy regimen, including adjuvant treatment

               -  Prior treatment with adjuvant chemotherapy is allowed and not counted as a
                  regimen

          -  Symptomatic pleural effusions should be drained prior to study entry

               -  No symptomatic serosal effusion (≥ CTCAE v3.0 grade 2 dyspnea) that is not
                  amenable to drainage prior to study entry

          -  Stable brain metastasis allowed provided the following criteria are met:

               -  Treated with either whole brain radiotherapy or gamma knife surgery

               -  More than 4 weeks since prior steroids

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  Life expectancy ≥ 12 weeks

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9 g/dL

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal

          -  Creatinine clearance ≥ 45 mL/min

          -  AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)

          -  INR < 1.5 OR PT/PTT normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 2 weeks after
             completion of study treatment

          -  Able to take folic acid, cyanocobalamin, and dexamethasone

          -  No clinically significant infection

          -  No known HIV positivity

          -  No evidence or history of bleeding diathesis or coagulopathy

          -  No serious nonhealing wound, ulcer, or bone fracture

          -  No significant traumatic injury within the past 4 weeks

          -  No bleeding ≥ grade 2 (except grade 2 petechiae) within the past 4 weeks

          -  No second primary malignancy except carcinoma in situ of the cervix or nonmelanomatous
             skin cancer, unless malignancy was diagnosed and definitively treated ≥ 5 years ago
             with no subsequent evidence of recurrence

               -  History of low-grade (Gleason score ≤ 6) localized prostate cancer allowed

               -  Patients with a history of DCIS that has been definitively treated will be
                  eligible even if diagnosed < 5 years prior to registration

          -  No other severe underlying disease or condition that, in the opinion of the
             investigator, would preclude study compliance or increase risk for serious adverse
             events

          -  Able to swallow pills

          -  No concurrent severe and/or uncontrolled medical conditions, including any of the
             following:

               -  Uncontrolled blood pressure, defined as systolic blood pressure (BP) > 150 mm Hg
                  and/or diastolic BP > 100 mm Hg, in spite of adequate antihypertensive therapy

               -  Angina pectoris

               -  Congestive heart failure within the past 3 months, unless LVEF > 40%

               -  Myocardial infarction within the past 6 months

               -  Cardiac arrhythmia

               -  Diabetes mellitus

               -  Active hemoptysis

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from all prior therapy, except for alopecia

          -  No prior sorafenib tosylate or pemetrexed disodium

          -  No prior therapy with agents that target VEGF, VEGF receptor, or VEGF receptor
             tyrosine kinase inhibitor (prior bevacizumab is allowed)

          -  Prior radiotherapy allowed if all the following criteria are met:

               -  No more than 25% of bone marrow was irradiated

               -  Measurable disease, whether there is in-field disease progression/recurrence or
                  disease outside the treatment fields of radiation port, is present

          -  No acetylsalicylic acid dose of ≥ 1.3 grams/day for ≥ 10 days before and after
             completion of study treatment

          -  At least 4 weeks since prior full-field radiotherapy

          -  At least 2 weeks since prior limited-field radiotherapy

          -  At least 4 weeks since prior major surgery (i.e., laparotomy) or open biopsy

          -  At least 2 weeks since prior minor surgery

          -  At least 3 weeks since prior chemotherapy (6 weeks for mitomycin C and nitrosoureas)

          -  At least 2 weeks since prior immunotherapy, biologic therapy, or gene therapy

          -  At least 4 weeks prior hormonal therapy

          -  At least 4 weeks since other prior investigational agents

          -  No concurrent antiretroviral therapy

          -  No concurrent major surgery

          -  No concurrent steroids

          -  No concurrent therapeutic anticoagulation

               -  Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) of venous or
                  arterial access devices allowed provided requirements for PT, INR, or PTT are met

          -  No concurrent Hypericum perforatum (St. John's wort)

          -  No concurrent grapefruit or grapefruit juice

          -  No concurrent prophylactic use of colony-stimulating factors

          -  No other concurrent anticancer agents or therapies