Multicenter Randomized Phase II Trial of Docetaxel With/Without VANDETANIB for Advanced Gastroesophageal Cancer

Inclusion 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