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Phase I Study of ZD6474 and Temozolomide in Patients With Advanced Cancer

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Study of ZD6474 and Temozolomide in Patients With Advanced Cancer


- To determine the maximum tolerated dose of concurrently administered vandetanib and
temozolomide in patients with unresectable, advanced solid tumors.

- To describe the toxicity profile of this regimen in these patients.

- To describe the response rate in patients treated with this regimen.

- To describe the effects of therapy on angiogenesis-related translational endpoints.

OUTLINE: Patients receive escalating doses of oral vandetanib once daily on days 1-28 and
oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of
disease progression or unacceptable toxicity.

Blood samples are collected at baseline and prior to each treatment course for correlative
laboratory studies, including evaluation of plasma VEGF levels by ELISA, serum angiogenesis
assay, and measurement of circulating endothelial cell populations (CD133, CD34, CD146).
Frozen serum and plasma samples are also stored for future research studies.

Inclusion Criteria


- Histologically confirmed solid tumor

- Unresectable, advanced disease

- Measurable or evaluable disease

- No known standard therapy that is potentially curative or definitely capable of
extending life expectancy exists

- No intracranial metastatic disease, unless it has been radiologically and clinically
stable for the past 3 months


- ECOG performance status 0-2

- ANC ≥ 1,500/μL

- Absolute lymphocyte count > 1,000/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin ≥ 8.0 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 3 times ULN (≤ 5 times ULN if liver involvement)

- Creatinine ≤ 1.5 times ULN OR creatinine clearance > 50 mL/min

- Potassium normal

- Serum calcium (ionized or adjusted for albumin) normal

- Magnesium normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled infection

- No currently active diarrhea that results in an ongoing need for IV fluids and/or
that may affect the ability of the patient to absorb vandetanib or tolerate diarrhea

- No evidence of severe or uncontrolled systemic disease or any concurrent condition
that, in the opinion of the treating physician, makes it undesirable for the patient
to participate in the study or that would jeopardize compliance with the study

- No other malignancies within the past 5 years, except cervical carcinoma in situ or
adequately treated basal cell or squamous cell carcinoma of the skin

- No clinically significant cardiac event, such as myocardial infarction, NYHA class
II-IV heart disease within the past 3 months, or presence of cardiac disease that, in
the opinion of the treating physician, increases the risk of ventricular arrhythmia

- No history of arrhythmia (i.e., multifocal premature ventricular contractions,
bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation)
that is symptomatic or requires treatment (CTCAE grade 3)

- Atrial fibrillation that is controlled on medication allowed

- No asymptomatic sustained ventricular tachycardia

- No history of QTc prolongation as a result of other medication that required
discontinuation of that medication

- No congenital long QT syndrome

- No 1st degree relative with unexplained sudden death under 40 years of age

- No left bundle branch block

- No QTc with Bazett's correction that is unmeasurable

- QTc < 480 msec on screening ECG

- No hypertension that is uncontrolled by medical therapy (i.e., systolic blood
pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg)

- No bleeding diathesis (inherited coagulopathy)


- Recovered from prior therapy

- More than 30 days since prior investigational agents

- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)

- More than 4 weeks since prior immunotherapy or biologic therapy

- More than 4 weeks since prior major surgery

- Surgical incision must be completely healed

- More than 4 weeks since prior radiotherapy, except palliative radiotherapy

- No prior radiotherapy to > 25% of bone marrow

- No prior temozolomide or dacarbazine

- No prior enrollment in this study

- More than 2 weeks since prior and no concurrent known potent CYP3A4 inducers, such as
rifampin, phenytoin, carbamazepine, barbiturates, or St. John's wort

- More than 2 weeks since prior and no concurrent drugs associated with an increased
risk of causing Torsades de Pointes

- No concurrent medication that may cause QTc prolongation

- No concurrent anticoagulants

- No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary
therapy considered investigational

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of vandetanib and temozolomide

Safety Issue:


Principal Investigator

Ravi D. Rao, MD, MBBS

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic



Study ID:




Start Date:

January 2008

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific