NCT00533169

Brief Summary

The goal of this clinical research study is to find the highest safe dose of the drug ZactimaTM (ZD6474) in patients with neuroblastoma or medulloblastoma that has gotten worse, has come back, or has not responded to the treatment. Primary Objective:

  • To determine the pharmacokinetics, safety, dose-limiting toxicities, and maximum tolerated dose of ZD6474, alone in children with medulloblastoma, and alone in combination with retinoic acid, in patients with relapsed or refractory neuroblastoma. Secondary Objective:
  • To assess progression-free survival (PFS) and objective tumor response rates in children with relapsed and refractory neuroblastoma and medulloblastoma treated with ZD6474 +/- retinoic acid in the context of a Phase I trial.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2007

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2007

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

September 19, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 21, 2007

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2011

Completed
Last Updated

December 15, 2011

Status Verified

December 1, 2011

Enrollment Period

3.4 years

First QC Date

September 19, 2007

Last Update Submit

December 13, 2011

Conditions

Neuroblastoma

Keywords

NeuroblastomaZD6474ZactimaIsotretinoin13-Cis Retinoic AcidAccutanePediatric Neuroblastoma

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD)

    MTD is highest dose level in which 6 participants have been treated with at most 2 experiencing dose limiting toxicity (DLT).

    28 day cycles, first 2 cycles used to determine dose-limiting toxicity

Study Arms (1)

ZD6474 + Retinoic Acid

EXPERIMENTAL

Part A = ZD6474 Alone, Starting dose 50 mg/m\^2 by mouth daily for 28 days; Part B, C = ZD6474 + Retinoic Acid 80 mg/m\^2 by mouth twice daily for 2 consecutive weeks out of every four weeks (28 days).

Drug: ZD6474Drug: Retinoic Acid

Interventions

ZD6474DRUG

Part A = Starting dose 50 mg/m\^2 by mouth daily for 28 days; Part B, C = Starting dose 50 mg/m\^2 by mouth daily on days 2-28.

Also known as: Zactima, Vandetanib
ZD6474 + Retinoic Acid
Retinoic AcidDRUG

Part B, C = 80 mg/m\^2 by mouth twice daily for 2 consecutive weeks out of every four weeks (28 days).

Also known as: Isotretinoin, Accutane, 13-cis-Retinoic Acid
ZD6474 + Retinoic Acid

Eligibility Criteria

Age2 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of informed consent from subjects or their legal guardians
  • Patients must have had histologic verification of neuroblastoma, ganglioneuroblastoma, or ganglioneuroma, and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines (Vanillylmandelic Acid (VMA) and/or Homovanillic Acid (HVA)), OR histologic verification of medulloblastoma, AND which has progressed on standard therapy, relapsed after standard therapy, or for which no standard curative therapy is known.
  • Measurable or evaluable disease presence within 4 weeks of onset of study therapy: a. measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan or X-ray obtained prior to study entry. Patients who appear to have residual stable tumor upon completion of frontline therapy must undergo a biopsy to document presence of viable neuroblastoma or medulloblastoma. If only active target lesion was radiated of patients with stable disease, biopsy must be done at least 4 weeks after radiation was completed and must demonstrate viable tumor, OR
  • (Con't # 3): Evaluable disease documented by bone marrow obtained prior to study entry with tumor cells seen on routine morphology (not by Neuron Specific Enolase (NSE) staining only) of aspirate and/or biopsy OR
  • (Con't # 3) (for neuroblastoma patients only) Evaluable disease documented by MIBG (metaiodobenzylguanidine) scan or bone scan obtained within 4 weeks prior to study entry with positive uptake at a minimum of one site. Patients who appear to have residual stable MIBG positive lesions upon completion of frontline therapy must undergo a biopsy to document the presence of viable neuroblastoma. If the patient has only one MIBG positive lesion and that lesion was radiated, a biopsy must be done at least 4 weeks after radiation was completed and must demonstrate viable neuroblastoma.
  • Performance status - Lansky play or karnofsky score of \> / = 40
  • Age \>/=2 years at time of enrollment

You may not qualify if:

  • Lab results: a) Absolute neutrophil count (ANC) \<750/mm\^3, hemoglobin \<7.0 g/dL, platelets \<20,000/mm\^3 (hemoglobin and platelets may be supported by transfusions); b) Serum bilirubin \>1.5 \* institutional upper limit of normal (IULN); c) Serum creatinine \>1.5 \* per IULN or creatinine clearance \<or equal to 70 ml/min/1.73m\^2; d) Potassium, \<4.0 mmol/L despite supplement; Serum calcium or ionized calcium \>IULN; Magnesium out of normal range per institutional guidelines despite supplement; e) ALT \> 2.5 \* IULN or alkaline phosphatase (ALP) \>2.5 \* IULN or \> 5 \* IULN if judged by the investigator to be related to liver metastases
  • 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.
  • History of symptomatic or medically managed arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) (\>/= National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation controlled on medication is not excluded.
  • Previous history of Corrected QT (QTc) prolongation as a result from other medication 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
  • QTc with Bazett's correction that is unmeasurable, or \>/=480 msec on screening Electrocardiography (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 QTc from the three screening ECGs must be \<480 msec in order for the patient to be eligible for the study.
  • Use of any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
  • Clinically significant cardiac event such as myocardial infarction, TIA, or CVA within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
  • Hypertension \> 95th percentile for age (either systolic or diastolic) or \> 140/90 for patients \>18 years of age and uncontrolled by oral medication at onset of study therapy.
  • Currently active diarrhea that may affect the ability of the patient to absorb the ZACTIMA.
  • Women who are currently pregnant or breastfeeding.
  • Receipt of any investigational agents within 14 days prior to commencing study treatment, or prior receipt of ZACTIMA at any time
  • Last dose of prior chemotherapy discontinued less than 2 weeks before the start of study therapy.
  • Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy to non-index lesions
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

Neuroblastoma

Interventions

vandetanibTretinoinIsotretinoin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Vitamin ARetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesDiterpenesPigments, BiologicalBiological Factors

Study Officials

  • Peter E. Zage, MD, PhD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 19, 2007

First Posted

September 21, 2007

Study Start

September 1, 2007

Primary Completion

February 1, 2011

Study Completion

February 1, 2011

Last Updated

December 15, 2011

Record last verified: 2011-12

Locations

US(1)