Docetaxel With or Without Vandetanib in Treating Patients With Metastatic Stomach Cancer or Gastroesophageal Junction Cancer
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: docetaxel; vandetanib
Intervention description: Given IV once every 3 weeks; Oral vandetanib once daily
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: recurrent gastric cancer; stage IV gastric cancer; adenocarcinoma of the stomach

Summary:

      RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Vandetanib 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 docetaxel is more
      effective when given together with or without vandetanib.

      PURPOSE: This randomized phase II trial is studying docetaxel to see how well it works
      compared with docetaxel given together with vandetanib in treating patients with metastatic
      stomach cancer or gastroesophageal junction cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed gastric adenocarcinoma or gastroesophageal junction cancer

               -  Metastatic disease

          -  Measurable disease

          -  No symptomatic CNS metastases

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  ECOG performance status 0-1

          -  Life expectancy ≥ 3 months

          -  ANC ≥ 1,500/µL

          -  Platelet count ≥ 100,000/µL

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  Creatinine < 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

          -  Potassium ≥ 4.0 mEq/L (supplementation allowed) and ≤ the CTCAE grade 1 upper limit

          -  Magnesium normal (supplementation allowed) and ≤ the CTCAE grade 1 upper limit

          -  Calcium normal and corrected serum calcium ≤ the CTCAE grade 1 upper limit

               -  In cases where the serum calcium is below the normal range, calcium (adjusted for
                  albumin) normal OR ionized calcium normal

          -  ALT and AST ≤ 2.5 times ULN

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for up to 12 weeks after
             completion of study therapy

          -  Atrial fibrillation allowed if controlled by medication

          -  LVEF ≥ 45% by MUGA or ECHO

        Exclusion criteria:

          -  Evidence of severe or uncontrolled systemic disease

          -  Any concurrent condition which makes it undesirable for the patient to participate in
             the trial or which would jeopardize study compliance, in the Investigator's opinion

          -  Uncontrolled infection

          -  Coagulopathy (including warfarin or anti-coagulant related) or bleeding disorder

          -  Peripheral neuropathy ≥ grade 2

          -  Clinically significant cardiac event, including myocardial infarction or New York
             Heart Association class II-IV heart disease within the past 3 months

          -  Presence of cardiac disease that, in the opinion of the Investigator, increases the
             risk of ventricular arrhythmia

          -  History of arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy,
             trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is
             symptomatic or requires treatment (CTCAE grade 3) OR asymptomatic sustained
             ventricular tachycardia

          -  History of QTc prolongation as a result of other medication that required
             discontinuation of that medication

          -  Congenital long QT syndrome or a first degree relative with unexplained sudden death
             under 40 years of age

          -  Presence of left bundle branch block

          -  QTc with Bazett's correction that is unmeasurable or ≥ 480 msec on screening ECG

               -  If a patient has QTc ≥ 480 msec on screening ECG, the screen ECG may be repeated
                  twice (at least 24 hours apart)

               -  The average OTc from the three screening ECGs must be < 480 msec in order for the
                  patient to be eligible for the study

          -  Hypertension not controlled by medical therapy (systolic blood pressure [BP] > 160 mm
             Hg or diastolic BP > 100 mm Hg)

          -  Currently active diarrhea (≥ grade 2) that may affect the ability of the patient to
             absorb vandetanib

          -  Previous or current malignancies of other histologies within the past 5 years, with
             the exception of cervical carcinoma in situ and adequately treated basal cell or
             squamous cell carcinoma of the skin

        PRIOR CONCURRENT THERAPY:

          -  Recovered from all prior therapy

          -  At least 4 weeks since prior chemotherapy or radiotherapy

          -  No more than one prior chemotherapy regimen for metastatic disease

               -  Prior adjuvant therapy, including chemoradiotherapy, allowed

          -  At least 2 weeks since prior palliative radiotherapy

               -  Up to 3750 cGy palliative radiotherapy to the stomach allowed

          -  No prior therapy with docetaxel

          -  More than 30 days since prior investigational agents

          -  More than 4 weeks since prior and no concurrent or planned participation in another
             experimental drug study

          -  More than 4 weeks since prior major surgery and recovered

          -  More than 2 weeks since prior and no concurrent medication that may cause QTc
             prolongation or induce Torsades de Pointes

          -  No concurrent amiodarone

          -  No concurrent potent inducers of CYP3A4 function (e.g., rifampicin, rifabutin,
             phenytoin, carbamazepine, barbiturates, or Hypericum perforatum [St. John wort])

          -  No prior enrollment or randomization to treatment in the present study