Gemcitabine and Carboplatin With or Without AZD2171 as First-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: carboplatin; cediranib maleate; gemcitabine hydrochloride
Intervention description: Given IV; Given orally; Given IV
Intervention MeSH terms: Carboplatin; Gemcitabine; Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 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; squamous cell lung cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. AZD2171 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. Giving gemcitabine and carboplatin
      together with AZD2171 may kill more tumor cells.

      PURPOSE: This randomized phase II trial is studying how well giving gemcitabine and
      carboplatin together with AZD2171 works compared to giving gemcitabine and carboplatin
      without AZD2171 as first-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-small cell lung cancer (NSCLC)

               -  Squamous cell histology allowed

               -  No mixed histology with small cell component

          -  Stage IIIB (with pleural effusion) or stage IV disease

               -  Presence of peritoneal or pericardial effusion alone in the absence of cytologic
                  evidence is not allowed

          -  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 only site of measurable disease was previously irradiated, progressive
                  disease must be evident

          -  Ineligible for bevacizumab therapy

          -  No symptomatic, untreated, or uncontrolled CNS metastases

               -  CNS metastases treated with whole-brain radiation (WBRT) allowed 4 weeks after
                  completion of WBRT

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  Life expectancy ≥ 12 weeks

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Hemoglobin ≥ 9 g/dL

          -  Platelet count ≥ 100,000/mm^3

          -  Bilirubin ≤ 3 times upper limit of normal (ULN)

          -  ALT and AST ≤ 3 times ULN (5 times ULN if liver involvement)

          -  Alkaline phosphatase ≤ 5 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective nonhormonal contraception

          -  No proteinuria ≥ 1+

          -  No uncontrolled blood pressure (BP), defined as systolic BP > 150 mm Hg and/or
             diastolic BP > 100 mm Hg in spite of adequate antihypertensive therapy

          -  No impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of AZD2171 (e.g., ulcerative disease, uncontrolled
             nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection)

          -  No seizure disorder

          -  No significant traumatic injury within 4 weeks prior to study entry

          -  No second primary malignancy except any of the following:

               -  Carcinoma in situ of the cervix

               -  Nonmelanoma skin cancer

               -  Prior malignancy diagnosed and definitively treated ≥ 5 years ago with no
                  subsequent evidence of recurrence

               -  History of low-grade (Gleason score ≤ 6) localized prostate cancer even if
                  diagnosed < 5 years prior to registration

               -  Treated stage I breast cancer ≤ 5 years prior to registration

          -  No uncontrolled intercurrent illness, including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Significant pulmonary symptoms at baseline due to disease

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness or social situation that would limit compliance with study
                  requirements

               -  Baseline hemoptysis

               -  Cavitating lesions

          -  No QTc prolongation > 500 msec or other significant ECG abnormality within the past 14
             days

          -  No New York Heart Association class III or IV disease

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior chemotherapy for advanced lung cancer

               -  Neoadjuvant or adjuvant therapy for lung cancer within the past 12 months allowed

          -  More than 12 months since prior immunotherapy and biologic therapy

          -  More than 4 weeks since prior radiotherapy (2 weeks for palliative radiotherapy to
             skeletal metastases)

          -  At least 2 weeks since prior WBRT

          -  No radiotherapy to ≥ 25% of bone marrow

          -  No major surgery (i.e., laparotomy) or open biopsy within 4 weeks prior to study entry
             (2 weeks for minor surgery)

               -  Insertion of a vascular access device not considered major or minor surgery

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No concurrent grapefruit or grapefruit juice during AZD2171 treatment

          -  No concurrent drugs or biologics with proarrhythmic potential

          -  Concurrent palliative radiotherapy to nontarget sites (i.e., painful pre-existing bony
             metastasis) allowed with AZD2171 (chemotherapy is held until completion of
             radiotherapy)