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A Phase II Study of Vandetanib in Patients With Non-small Cell Lung Cancer Harboring RET Rearrangement

Phase 2
18 Years
Open (Enrolling)
Non Small Cell Lung Cancer

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Trial Information

A Phase II Study of Vandetanib in Patients With Non-small Cell Lung Cancer Harboring RET Rearrangement

Patients will be screened so as to confirm RET fusion in their tumor tissue. RET fusion will
be tested using fluorescence in situ hybridization (FISH) at central laboratory. Central
laboratory of this study is the department of pathology at Seoul National University
Hospital (SNUH) and tumor specimen should be sent to department of pathology at SNUH. Only
patients whose tumor have confirmed RET gene fusion are eligible for this study.

Enrolled patients will begin on once daily vandetanib at 300 mg with one cycle of 4 weeks.
Renal-impaired patients (defined as patients with creatinine clearance ≥30 to <50 mL/min at
screening) will start treatment at the lower dose of 200 mg. Treatment will be continued
till progression, unacceptable toxicity, or till 1 year. Vandetanib can be administered
after 1 year to the patients with benefit from vandetanib.

During the administration of vandetanib, vital signs, physical examination, ECOG performance
status, height, weight, hematology and chemistry test, ECG, adverse events and concomitant
drugs will be evaluated every four weeks (one cycle, for the first 6 months) or eight weeks
(two cycles, from 6 months to 1 year) and, if necessary, chest X-ray and pregnancy test will
also be performed. CT for tumor assessment will be performed once every 8 weeks for 1 year.
If the disease progression is suspected, the test can be additionally conducted at the
investigator's discretion.

Inclusion Criteria:

- Provision of informed consent

- Female or male aged 18 years or over

- Histologically confirmed locally advanced or metastatic (stage IIIB or IV) NSCLC

- Failure after platinum-based chemotherapy

- Presence of a RET fusion in an archival or newly acquired NSCLC tumor specimen (RET
fusion should be performed in central laboratory by FISH)

- ECOG performance status of 0, 1 or 2

- Negative pregnancy test (urine or serum) for female patients of childbearing

- Measurable disease according to RECIST 1.1 criteria

- Life expectancy of >12 weeks

- Able to swallow study medication

- If the subject is on the course of radiotherapy, one can be enrolled after

Exclusion Criteria:

- Involvement in the planning/conduct of this study

- Previous enrollment in the present study

- Previous exposure to vandetanib

- Unstable brain metastases or spinal cord compression that requires treatment (The
patients with treated brain metastases who are on a stable dose of steroids can be

- Major surgery within 28 days before starting treatment

- The last dose of prior chemotherapy received less than 28 days prior to starting

- Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer

- Serum bilirubin greater than 1.5 x the upper limit of reference range (ULRR)

- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline
phosphatase (ALP) greater than 2.5 x ULRR, or greater than 5.0 x ULRR if judged by
the investigator to be related to liver metastases

- Creatinine clearance <30 mL/min (Patients with moderate renal impairment defined as
screening creatinine clearance ≥30 to <50 mL/min will start vandetanib at a reduced
dose of 200 mg once daily and will continue this dose throughout the study, unless
further dose reduction is required)

- Unacceptable electrolyte imbalance (Potassium <4.0 mmol/L despite supplementation,
Magnesium below normal range despite supplementation, Calcium as evaluated by either
ionized or standard serum tests: ionized calcium below the normal range or serum
calcium above the CTCAE grade I upper limit)

- Significant cardiac event (e.g. myocardial infarction), superior vena cava syndrome,
NYHA classification of heart disease ≥2 within 12 weeks before starting treatment, or
presence of cardiac disease that in the opinion of the investigator increases the
risk of ventricular arrhythmia

- History of ventricular arrhythmia, which is symptomatic or requires treatment (CTCAE
grade 3), symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained
ventricular tachycardia. (Patients with atrial fibrillation controlled by medication
are permitted)

- Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood
pressure > 100 mmHg)

- Past medical history of, or clinically active interstitial lung disease

- Evidence of severe or uncontrolled systemic disease

- Previous or current malignancies of other histologies within the last 3 years. (In
situ carcinoma of the cervix, adequately treated basal cell or squamous cell
carcinoma of the skin is exceptionally permitted)

- Congenital long QT syndrome

- Any concomitant medications that are known to be associated with Torsades de Pointes
or potent inducers of cytochrome P450 3A4 (CYP3A4) function and/or any prohibited

- History of QT prolongation associated with other medication that required
discontinuation of that medication

- QTcB correction unmeasurable or >480 ms on screening ECG

- Participation in a clinical study and/or receipt of an investigational drug within 28
days prior to enrollment

- Females only - currently pregnant or breast feeding

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate (ORR)

Outcome Description:

ORR will be evaluated through the frequency analysis with 95% confidence interval.

Outcome Time Frame:

1 year

Safety Issue:



Korea: Food and Drug Administration

Study ID:




Start Date:

April 2013

Completion Date:

September 2016

Related Keywords:

  • Non Small Cell Lung Cancer
  • Lung cancer
  • RET fusion
  • Vandetanib
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms