Overview

Study of GemOx and Vandetanib in Advanced Solid Malignancy

Status:
Completed
Trial end date:
2010-12-01
Target enrollment:
0
Participant gender:
All
Summary
This is a research study that will try to find the highest and safest dose of an experimental drug, vandetanib, that can be given in combination with two standard chemotherapy agents, gemcitabine and oxaliplatin, to subjects with advanced solid malignancies.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Leonard Appleman
Collaborator:
AstraZeneca
Treatments:
Gemcitabine
Oxaliplatin
Criteria
Inclusion Criteria:

- Patients with advanced incurable solid malignancy who are likely to benefit from GEMOX
therapy.

- Provision of informed consent prior to any study procedures.

- Females and males age ≥18 years

- Histological/cytological confirmation of malignancy

- Negative pregnancy test for women of childbearing potential

- ECOG performance status of 0 or 1

- Ability to take oral medications without difficulty

- Adequate bone marrow function: ANC >1500/L and platelet count >100,000/dL

- Adequate hepatic function: Total Bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 2.5 x ULN (≤ 5 x ULN
in case of liver metastasis), ALP ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)

- Serum calcium in normal range (ionized or adjusted for albumin), Serum magnesium in
normal range, Serum Potassium ≥ 4.0 mmol/L. Supplementation allowed.

- Serum Cr < 1.5 x UNL or Creatinine Clearance ≥ 50 mL/min calculated by Cockcroft-Gault
formula

- Men and women of childbearing potential must be willing to practice acceptable methods
of birth control.

- Patients with brain metastasis should have received appropriate therapy and have
stable disease at least 4 weeks after radiotherapy/surgery.

- Subjects should have recovered from side effects of prior therapy to grade 1 or less

Exclusion Criteria:

- Evidence of severe or uncontrolled systemic disease or any concurrent condition which
in the Investigator's opinion makes it undesirable for the patient to participate in
the trial or which would jeopardize compliance with the protocol.

- Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena
cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease
≥2 within 3 months before entry; or presence of cardiac disease that, in the opinion
of the Investigator, increases the risk of ventricular arrhythmia.

- History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy,
trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is
symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained
ventricular tachycardia. Atrial fibrillation, controlled on medication is not
excluded.

- Previous history of QTc prolongation with other medications that required
discontinuation of that medication.

- Congenital long QT syndrome or 1st degree relative with unexplained sudden death under
40 years of age.

- Presence of left bundle branch block (LBBB.)

- QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG.
(Note: If a subject has a QTc interval ≥480 msec on screening ECG, the screen ECG may
be repeated twice (at least 24 hours apart). The average QTc from the three screening
ECGs must be <480 msec in order for the subject to be eligible for the study.)
Patients who are receiving a drug that has a risk of QTc prolongation are excluded if
QTc is ≥ 460 msec.

- Any concurrent medication that may cause QTc prolongation or induce Torsades de
Pointes.

- Hypertension not controlled by medical therapy (systolic blood pressure greater than
160 mm Hg or diastolic blood pressure greater than 100 mm Hg)

- Currently active diarrhea that may affect the ability of the patient to absorb the
vandetanib or tolerate diarrhea.

- Women who are currently pregnant or breast feeding.

- Receipt of any investigational agents within 30 days or commercially available agents
within 21 days prior to commencing study treatment

- Last dose of prior chemotherapy discontinued less than 4 weeks before the start of
study therapy

- Last radiation therapy within the last 4 weeks before the start of study therapy,
except palliative radiotherapy for less than 12 fractions

- Any unresolved toxicity greater than CTCAE grade 1 from previous anti-cancer therapy

- Previous enrollment or randomization of treatment in the present study

- Major surgery within 4 weeks, or incompletely healed surgical incision before starting
study therapy

- Peripheral neuropathy grade 2 or of greater severity of any cause

- More than 2 prior systemic chemotherapy regimens for advanced stage disease. Prior
adjuvant chemotherapy will not count as a prior regimen.

- Known severe hypersensitivity to vandetanib or any of the excipients of these
products.

- Previous or current malignancies of other histologies within the last 5 years, with
the exception of cervical carcinoma in situ and adequately treated basal cell or
squamous cell carcinoma of the skin.

- Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin,
carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.