Pemetrexed, Carboplatin, and Bevacizumab as First-Line Therapy in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: bevacizumab; carboplatin; pemetrexed disodium
Intervention MeSH terms: Bevacizumab; Carboplatin; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 70 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer; adenocarcinoma of the lung; adenosquamous cell lung cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways.
      Some block the ability of tumor cells to grow and spread. Others find tumor cells and help
      kill them or carry tumor-killing substances to them. Giving pemetrexed together with
      carboplatin and bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving pemetrexed together with carboplatin
      and bevacizumab works as first-line therapy in treating older patients with stage IIIB or
      stage IV non-small cell lung cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed nonsquamous cell non-small cell lung cancer
             (NSCLC)

               -  Stage IIIB (with pleural effusion) or IV disease

               -  Squamous cell carcinomas not allowed

                    -  Adenosquamous histology allowed

          -  Clinically significant effusion (e.g., symptomatic pleural effusion or ascites)
             allowed provided it is drained before study treatment

               -  No symptomatic pleural and/or peritoneal effusion (≥ grade 2 dyspnea, as defined
                  by NCI CTCAE v3.0 criteria) that is not amenable to drainage

               -  If effusion produces clinically significant measurable objective changes, such as
                  hypoxia or estimated volume > 500 mL, effusion should be drained even if
                  asymptomatic

          -  Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by
             conventional techniques or ≥ 1.0 cm by spiral CT scan

               -  If the sole site of disease is in a previously irradiated field, must have
                  evidence of disease progression/recurrence within the irradiated field OR
                  presence of a new lesion outside the irradiated field

          -  No symptomatic, untreated, or uncontrolled CNS metastases

               -  CNS metastases that were previously treated with whole brain radiotherapy (WBRT)
                  allowed

          -  Willing to enroll in NCCTG-N0392

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  Life expectancy ≥ 12 weeks

          -  ANC ≥ 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

          -  AST and ALT ≤ 3 times ULN (≤ 5 times ULN if liver has tumor involvement)

          -  Creatinine clearance ≥ 45 mL/min

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception during and for 3 months after
             completion of study treatment

          -  Able to take folic acid, vitamin B_12 supplementation, or dexamethasone

          -  Able to complete questionnaire(s) alone or with assistance

          -  Willing to provide biologic specimens as required by the study

          -  Willing to return to NCCTG participating center for follow-up

          -  No clinically significant infection

          -  No serious, nonhealing wounds, ulcers, or bone fractures

          -  No seizure disorder

          -  No second primary malignancy within the past 5 years, except for any of the following:

               -  Carcinoma in situ of the cervix

               -  Nonmelanomatous skin cancer

                    -  History of melanoma allowed only if diagnosed and definitively treated ≥ 5
                       years ago with no subsequent evidence of recurrence

               -  Low-grade (Gleason score ≤ 6) localized prostate cancer (no nodal involvement)

               -  Previously treated stage I breast cancer

          -  No concurrent severe and/or uncontrolled medical condition, including any of the
             following:

               -  Hypertension, labile hypertension, or history of poor compliance with
                  antihypertensive medication

               -  Angina pectoris

               -  Congestive heart failure within the past 3 months, unless ejection fraction > 40%

               -  Myocardial infarction within the past 6 months

               -  Cardiac arrhythmia

               -  Diabetes mellitus

               -  Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the
                  lung

               -  Active or recent history of hemoptysis > ½ teaspoon per event

               -  Ongoing or active infection

               -  Psychiatric illness/social situation that would limit compliance with study
                  requirements

          -  No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
             the past 12 months

          -  No diverticulitis within the past 12 months

          -  No stroke within the past 6 months

          -  No significant traumatic injury within the past 8 weeks

          -  Not at greater than normal risk of bleeding

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior radiotherapy to > 25% of bone marrow

          -  More than 2 weeks since prior radiotherapy and recovered (alopecia allowed)

          -  At least 2 weeks since prior WBRT

          -  At least 3 days since prior gamma knife radiosurgery (without WBRT) for brain
             metastases

          -  More than 4 weeks since prior administration of live or attenuated viral vaccine

          -  More than 8 weeks since prior major surgery (e.g., laparotomy) or open biopsy (> 4
             weeks since minor surgery)

               -  Insertion of a vascular access device allowed

          -  No prior chemotherapy or systemic therapy for advanced lung cancer, except neoadjuvant
             or adjuvant chemotherapy

          -  No NSAID's 2 days prior to (5 days for long-acting NSAID's), the day of, and 2 days
             following protocol treatment

          -  More than 12 months since prior neoadjuvant therapy, adjuvant therapy, systemic
             chemotherapy, chemoradiotherapy, immunotherapy, or biologic therapy

          -  No concurrent anticoagulants

               -  Low-dose warfarin or heparin for deep venous thrombosis prophylaxis allowed