Clinical trial NCT00683787: Docetaxel With or Without Vandetanib in Treating Patients With Metastatic Stomach Cancer or Gastroesophageal Junction Cancer
Official title: Multicenter Randomized Phase II Trial of Docetaxel With/Without VANDETANIB for Advanced Gastroesophageal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: recurrent gastric cancer
stage IV gastric cancer
adenocarcinoma of the stomach
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2008-05-23
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: OBJECTIVES:

Primary

* To test the hypothesis that the addition of a targeted agent, such as vandetanib, to standard chemotherapy with docetaxel will result in incremental responses in patients with metastatic gastric or gastroesophageal junction cancer.

Secondary

* To assess progression-free survival and overall survival of patients treated with this regimen.
* To study the toxicity profile of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical site. Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive docetaxel IV once every 3 weeks.
* Arm II: Patients receive docetaxel IV as in arm I and oral vandetanib (100 mg) once daily.
* Arm III: Patients receive docetaxel IV as in arm I and oral vandetanib (300 mg) once daily.

In all arms, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2 months for 5 years.

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

Primary outcomes:
measure: Overall Response Rate
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 3 years
measure: Overall Survival
timeFrame: 3 years
measure: Toxicity
timeFrame: 1 year
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Nikhil Khushalani, MD
role: PRINCIPAL_INVESTIGATOR
References: