Vandetanib in Advanced NSCLC With RET Rearrangement

NCT01823068 | Completed Phase 2 DMC

• 1 other identifier: 2013-09-089-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Non Small Cell Lung Cancer

Keywords

Lung cancer; RET fusion; Vandetanib

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

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

  1 year

Secondary Outcomes (4)

• Progression-free survival (PFS)

  1 year

• Disease-control rate (DCR)

  1 year

• Overall survival (OS)

  2 years

• Number of Participants with Adverse Events

  1 years

Study Arms (1)

Vandetanib treatment arm

EXPERIMENTAL

Vandetanib 300 mg once daily orally

Drug: Vandetanib

Interventions

Vandetanib DRUG

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

Also known as: Caprelsa

Vandetanib treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Samsung Medical Center: lead
• AstraZeneca: collaborator

Study Sites (2)

Seoul National University Hospital

Seoul, 110744, South Korea

Location

Samsung Medical Center

Seoul, 135710, South Korea

Location

Related Publications (7)

• 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.

  PMID: 22194472 BACKGROUND

• 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.

  PMID: 22327623 BACKGROUND

• 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.

  PMID: 22327622 BACKGROUND

• 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.

  PMID: 23584301 BACKGROUND

• 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.

  PMID: 25366691 BACKGROUND

• 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.

  PMID: 27803005 DERIVED

• 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.

  PMID: 26291023 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

vandetanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 22, 2013
• First Posted: April 4, 2013
• Study Start: November 3, 2014
• Primary Completion: December 29, 2014
• Study Completion: March 16, 2018
• Last Updated: December 7, 2020

Record last verified: 2020-12

Locations

KR (2)