AZD2171 + Chemotherapy in Advanced NSCLC, Colorectal Cancer, or Other Cancer Suitable for Treatment With Capecitabine (Non-Small Lung Cancer Patients Closed to Enrollment as 8/9/07)
Condition: Colorectal Cancer; Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Lung Neoplasms; Colorectal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: 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. Drugs used in chemotherapy, such as
      paclitaxel, carboplatin, or capecitabine, work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Giving AZD2171 together
      with chemotherapy may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of AZD2171 when given
      together with chemotherapy in treating patients with advanced non-small cell lung cancer
      (closed to enrollment as of 8/9/07), colorectal cancer, or other cancer suitable to
      capecitabine treatment.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the maximum tolerated dose and recommended phase II dose of AZD2171 when
           administered in combination with standard chemotherapy comprising either paclitaxel and
           carboplatin OR capecitabine in patients with advanced incurable non-small cell lung
           cancer (closed to accrual as of 8/9/07), colorectal cancer, or other tumor types
           suitable for treatment with capecitabine.

        -  Determine the safety and tolerability of these regimens in these patients.

        -  Determine the toxicity profile and dose-limiting toxic effects of these regimens in
           these patients.

        -  Determine the pharmacokinetic profile of these regimens in these patients.

        -  Correlate the toxicity profile with the pharmacokinetic profile of these regimens in
           these patients.

        -  Determine the antitumor activity of these regimens in patients with measurable disease.

        -  Correlate patient outcome (response) with baseline (using tumor samples) and serial
           (using urine and plasma samples) biomarkers in patients treated with these regimens.

      OUTLINE: This is an open-label, multicenter, dose-escalation study of AZD2171. Patients are
      assigned to 1 of 2 treatment groups according to diagnosis.

        -  Group 1 (non-small cell lung cancer) (closed to accrual as of 8/9/07): Patients receive
           paclitaxel IV and carboplatin IV on day 1. Patients also receive oral AZD2171 once daily
           on days 2-21 of course 1 and on days 1-21 of all subsequent courses. Treatment with
           paclitaxel and carboplatin repeats every 21 days for up to 8 courses in the absence of
           disease progression or unacceptable toxicity. Treatment with AZD2171 repeats every 21
           days in the absence of disease progression or unacceptable toxicity.

        -  Group 2 (colorectal or other tumor types): Patients receive oral capecitabine twice
           daily on days 1-14. Patients also receive oral AZD2171 once daily on days 8-21 of course
           1 and on days 1-21 of all subsequent courses. Treatment with capecitabine repeats every
           21 days for up to 6 courses in the absence of disease progression or unacceptable
           toxicity. Treatment with AZD2171 repeats every 21 days in the absence of disease
           progression or unacceptable toxicity.

      In both groups, patients achieving a complete response (CR) OR a stable partial response
      (SPR) receive 2 additional courses beyond CR or SPR.

      Cohorts of 3-6 patients per group receive escalating doses of AZD2171 until the maximum
      tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
      of 6 patients experience dose-limiting toxicity. Up to 30 additional patients (20 in group 1
      and 10 in group 2) will be treated at the MTD.

      After completion of study treatment, patients are followed at 4 weeks and then every 3 months
      until disease relapse.

      PROJECTED ACCRUAL: A total of 3-35 patients will be accrued for this study.
    

Intervention name(s): capecitabine; carboplatin; cediranib maleate; paclitaxel
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 1000 mg/m2 orally twice daily (total of 2000 mg/m2 per day) for the first 14 days of a 21 day cycle for a maximum of 6-8 cycles.; AUC 6; IV; 30 minutes; Every 21 days for a maximum of 6-8 cycles; Given daily; orally with approximately 240 ml of water whilst in an upright position; 200mg/m2; IV; 3 hours; Every 21 days for a maximum of 6-8 cycles
Intervention MeSH terms: Paclitaxel; Carboplatin; Capecitabine; Cediranib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; stage IV colon cancer; stage IV rectal cancer; unspecified adult solid tumor, protocol specific