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Non Small Cell Lung CancerPhase 2NCT01823068

Vandetanib in Advanced NSCLC With RET Rearrangement

A Phase 2 study testing Vandetanib in people with Non Small Cell Lung Cancer, run by Samsung Medical Center at 2 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to investigate the efficacy and safety of vandetanib, in patients with advanced non-small-cell lung cancer harboring RET gene rearrangement. In 2011, gene rearrangement between RET and KIF5B gene (fusion) was discovered in a young, male lung cancer patient. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Vandetanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesSouth Korea
Study dates
3 Nov 2014to 16 Mar 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • Negative pregnancy test (urine or serum) for female patients of childbearing potential
  • 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 radiotherapy

Who cannot join

  • 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 included)
  • Major surgery within 28 days before starting treatment
  • The last dose of prior chemotherapy received less than 28 days prior to starting treatment
Show all 23Show fewer
  • Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy
  • 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 medications
  • 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

Trial locations and contacts

2 sites in 1 country.

South Korea2 sites

  • Seoul National University Hospital

    Seoul, 110744

  • Samsung Medical Center

    Seoul, 135710

Other trials in South Korea

About this study

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

The purpose of this study is to investigate the efficacy and safety of vandetanib, in patients with advanced non-small-cell lung cancer harboring RET gene rearrangement. In 2011, gene rearrangement between RET and KIF5B gene (fusion) was discovered in a young, male lung cancer patient. The following studies showed that this gene rearrangement was critical for tumor initiation and maintenance. Of note, the growth and signaling properties mediated by KIF5B-RET were diminished after treatment with vandetanib.

Until now, RET rearrangements have been known in thyroid cancers. Vandetanib, a multi-kinase inhibitors with anti-RET activity, is an FDA-approved drug for the treatments of adults with metastatic medullary thyroid cancers who are ineligible for surgery and who have progressive or symptomatic disease. This study aimed to examine the efficacy and safety of this drug, for the treatment of advanced lung cancer harboring RET rearrangement.

Read the detailed description

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.

Being tested
Vandetanib
Keywords
Lung cancer, RET fusion, Vandetanib
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VandetanibDrug

    Also called Caprelsa

    Patients will begin on once daily vandetanib at 300 mg with one cycle of 4 weeks.

Study groups in NCT01823068
Study groupRoleWhat they receive
Vandetanib treatment armExperimentalVandetanib 300 mg once daily orally
Receives: Drug: Vandetanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate (ORR)

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

    Measured: 1 year

Secondary outcomes (4)

  1. Progression-free survival (PFS)

    PFS will be examined with Kaplan-Meier method.

    Measured: 1 year

  2. Disease-control rate (DCR)

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

    Measured: 1 year

  3. Overall survival (OS)

    OS will be examined with Kaplan-Meier method.

    Measured: 2 years

  4. Number of Participants with Adverse Events

    Regarding safety endpoints, all adverse events will be individually graded based on the CTCAE version 4.03. The number of participants with adverse events will be summarized using descriptive statistics.

    Measured: 1 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2013 (estimated)
  2. Study start3 Nov 2014
  3. Primary completion29 Dec 2014
  4. Study completion16 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01823068
Sponsor's protocol ID
2013-09-089-01
Status last verified
Dec 2020
First submitted
22 Mar 2013
Last updated
7 Dec 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK, Kim YT, Kim JI, Kang JH, Seo JS. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res. 2012 Mar;22(3):436-45. doi: 10.1101/gr.133645.111. Epub 2011 Dec 22.

    PubMed 22194472

  • Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.

    PubMed 22327623

  • Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Janne PA, Stephens PJ. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012 Feb 12;18(3):382-4. doi: 10.1038/nm.2673.

    PubMed 22327622

  • Gautschi O, Zander T, Keller FA, Strobel K, Hirschmann A, Aebi S, Diebold J. A patient with lung adenocarcinoma and RET fusion treated with vandetanib. J Thorac Oncol. 2013 May;8(5):e43-4. doi: 10.1097/JTO.0b013e31828a4d07. No abstract available.

    PubMed 23584301

  • Falchook GS, Ordonez NG, Bastida CC, Stephens PJ, Miller VA, Gaido L, Jackson T, Karp DD. Effect of the RET Inhibitor Vandetanib in a Patient With RET Fusion-Positive Metastatic Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 May 20;34(15):e141-4. doi: 10.1200/JCO.2013.50.5016. Epub 2014 Nov 3. No abstract available.

    PubMed 25366691

  • Lee SH, Lee JK, Ahn MJ, Kim DW, Sun JM, Keam B, Kim TM, Heo DS, Ahn JS, Choi YL, Min HS, Jeon YK, Park K. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial. Ann Oncol. 2017 Feb 1;28(2):292-297. doi: 10.1093/annonc/mdw559.

    PubMed 27803005

  • Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.

    PubMed 26291023

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vandetanib in people with Non Small Cell Lung Cancer, run by Samsung Medical Center at 2 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01823068, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020; AzTrials last refreshed its copy on 6 Nov 2026.

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