Nintedanib(BIBF1120) in Thyroid Cancer
A Phase II Study Exploring the Safety and Efficacy of Nintedanib (BIBF1120) as Second Line Therapy for Patients With Either Differentiated or Medullary Thyroid Cancer Progressing After First Line Therapy.
2 other identifiers
interventional
100
9 countries
27
Brief Summary
For the treatment of thyroid cancer with the so called targeted therapy the angiogenesis pathway has several potential targets. The Receptors for Vascular endothelial growth factor (VEGF) and especially VEGFR-2 is considered to be crucial for the initiation of the formation as well as the maintenance of tumor vasculature. In thyroid cancer these VEGF receptors (VEGFR-1, VEGFR-2), VEGF itself and receptors of the fibroblast growth factor (FGF) and for the platelet-derived growth factor (PDGF) are often overexpressed. Other cells as pericytes and smooth muscle cells that are also involved in tumor angiogenesis express these receptors as well. Inhibitors of the VEGFR or PDGFR pathway have been tested in thyroid cancer with positive results. However there is no treatment that is generally considered as standard of care for patients with differentiated thyroid cancer (DTC) or medullar thyroid cancer (MTC) who have progressed on one line of therapy. The classical cytotoxic chemotherapy has not shown a clinically meaningful benefit yet. Nintedanib is a triple angiogenesis inhibitor which inhibits receptors of VEGF, FGF and PDGF. Therefore it might act not only on endothelial cells but also on pericytes and smooth muscle cells. Nintedanib also interacts with other kinases such as RET. Because of this multi-kinase activity rationale exists to investigate the effect in MTC and DTC. Because it targets these three major angiogenesis signaling pathways it might prevent further tumor growth and related tumor escape mechanisms. Therefore nintedanib may be active in patients who have progressed on agents that target only one pathway.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2014
Longer than P75 for phase_2
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 8, 2013
CompletedFirst Posted
Study publicly available on registry
February 11, 2013
CompletedStudy Start
First participant enrolled
May 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 28, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 28, 2019
CompletedJuly 31, 2020
July 1, 2020
5.3 years
February 8, 2013
July 30, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
This study will use RECIST 1.1 to measure PFS
2,5 years from FPI
Secondary Outcomes (4)
Occurence of Adverse Events
2,5 years from FPI
Response Rate
2,5 years from FPI
Duration of response
2,5 years form FPI
Exploration of the molecular mechanisms of action of drug
3 years from FPI
Study Arms (2)
Nintedanib
EXPERIMENTALNintedanib should be administered orally at a dose of 200 mg twice daily.
Placebo
PLACEBO COMPARATORPlacebo should be administered orally at a dose of 200 mg twice daily. Cross-over to nintedanib is allowed after progression.
Interventions
Nintedanib should be administered orally at a dose of 200 mg twice daily.
Eligibility Criteria
You may qualify if:
- Histologically confirmed differentiated or medullary thyroid cancer by local pathologist.
- Available tumor tissue at the time of initial diagnosis for histology review. The provision of tumor tissue for histology review is mandatory for every patient/site.
- Locally advanced or metastatic disease deemed incurable by surgery, radiotherapy and/or radioactive iodine (RAI).
- No current symptomatic brain metastases or if previously present, must have been treated at least two months before randomization. CT or MRI scan of the brain is mandatory (within 4 weeks prior to randomization) to assess the presence or not of brain metastases.
- Patients must have measurable lesion with documented progression during the 12 months prior to randomization, according to RECIST V.1.1. Patients who were withdrawn from first line treatment due to toxicity without documented disease progression or who received placebo (in the context of a clinical trial) as prior treatment are not eligible.
- Patients must have received one or 2 prior line of treatment (but no more than two) and must be off treatment for at least 4 weeks prior to randomization.
- Age ≥18 years.
- Performance status (PS) 0-1 (WHO, Appendix C).
- Life expectancy of more than 12 weeks.
- No history of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
- No ongoing treatment related toxicity due to prior treatment \> grade I (except alopecia).
- Adequate organ function, evidenced by the following laboratory results within 3 weeks prior to randomization: (patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry \[with the EXCEPTION of Glomerular Filtration Rate\] are acceptable)
- Absolute neutrophil count \> 1500 cells/mm3
- Platelet count \> 100,000 cells/mm3
- Hemoglobin \> 8.5 g/dL
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (27)
A.Z. St. Jan
Bruges, 8000, Belgium
Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet
Brussels, 1000, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Antwerpen, 2650, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
U.Z. Leuven - Campus Gasthuisberg
Leuven, 3000, Belgium
Odense University Hospital
Odense, 5000, Denmark
CHU d'Angers
Angers, 49933, France
Institut Bergonie
Bordeaux, 33076, France
Centre Regional Francois Baclesse
Caen, 14076, France
Centre Georges-Francois-Leclerc
Dijon, 21079, France
Centre Leon Berard
Lyon, 69008, France
Assitance Publique - Hopitaux de Paris - Hopital Saint-Louis
Paris, 75475, France
Assistance Publique - Hopitaux de Paris - La Pitié Salpétrière
Paris, 75651, France
Centre Jean Godinot
Reims, 51056, France
Institut Gustave Roussy
Villejuif, France
Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern
Munich, DE 81377, Germany
Universitaetsklinikum Wuerzburg
Würzburg, DE 97080, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Azienda Ospedaliera Universitaria "Federico II"
Napoli, 80131, Italy
University Medical Center Groningen
Groningen, 9713, Netherlands
Leiden University Medical Centre
Leiden, 2300, Netherlands
Radboud University Medical Center Nijmegen
Nijmegen, 6500, Netherlands
Maria Sklodowska-Curie Memorial Cancer Centre
Warsaw, PL 02 781, Poland
Hospital General Vall D'Hebron
Barcelona, ES 08035, Spain
Royal Marsden Hospital - Sutton, Surrey
Sutton, Surrey, SM2 5PT, United Kingdom
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
Glasgow, G12 0YN, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Martin Schlumberger, MD
Gustave Roussy, Cancer Campus, Grand Paris
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 8, 2013
First Posted
February 11, 2013
Study Start
May 1, 2014
Primary Completion
August 28, 2019
Study Completion
August 28, 2019
Last Updated
July 31, 2020
Record last verified: 2020-07