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Medullary Thyroid Cancer (MTC)Phase 2NCT01788982

Nintedanib(BIBF1120) in Thyroid Cancer

A Phase 2 study testing Nintedanib in people with Medullary Thyroid Cancer (MTC) and Differentiated Thyroid Cancer (DTC), run by European Organisation for Research and Treatment of Cancer - EORTC at 27 sites in 9 countries.

Completed

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

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nintedanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
100 participants
Where
27 sitesin 9 countries
Study dates
May 2014to 28 Aug 2019
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

  • 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 Patients who were withdrawn from first line treatment due to toxicity without documented disease progression or who received placebo (in the context of a clinical trial) as prior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.
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  • 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
  • Total bilirubin within normal limits
  • SGOT (AST), SGPT (ALT), and alkaline phosphatase ≤ 1.5× ULN (or ≤ 2.5× ULN) in the case of presence of liver metastases)
  • Glomerular Filtration Rate (GFR) ≥ 45 ml/min according to Cockcroft and Gault Formula (see Appendix E.).
  • Proteinuria CTC-AE < 2
  • Coagulation parameters: International normalized ratio (INR) ≤ 2, prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5x institutional ULN
  • No history of significant cardiac disease defined as:
  • Symptomatic CHF (NYHA classes III-IV, see Appendix D)
  • High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type 2 [Mobitz 2] or third degree AV-block)
  • No prolongation of corrected QT interval (QTc) > 480 msecs,
  • History of myocardial infarction within 12 months prior to randomization
  • Clinically significant valvular heart disease
  • No angina pectoris requiring anti-angina treatment
  • No current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg) (with or without medication). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
  • No evidence of active bleeding or bleeding diathesis.
  • No cerebrovascular accident at any time in the past, transient ischemic attack, deep venous thrombosis (DVT) or pulmonary embolism in the past 6 months.
  • Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day) is not allowed.
  • No history of clinically significant gastrointestinal disorders including: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation. No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.
  • No current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus) or any other systemic disease/symptoms that may hamper compliance to study protocol, according to physician's judgment.
  • No major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment and/or presence of any non-healing wound, fracture, or ulcer.
  • No history of receiving any investigational treatment within 28 days prior to randomization.
  • Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment.
  • Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  • Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
  • Tissue availability for central confirmation of the histological diagnosis is mandatory. All other TR projects are optional for the patient and a separate consent form for these will be provided to the patient.

Who cannot join

None listed.

Trial locations and contacts

27 sites in 9 countries.

27 sites in 9 countries

France9 sites

  • CHU d'Angers

    Angers, 49933

  • Institut Bergonie

    Bordeaux, 33076

  • Centre Regional Francois Baclesse

    Caen, 14076

  • Centre Georges-Francois-Leclerc

    Dijon, 21079

  • Centre Leon Berard

    Lyon, 69008

  • Assitance Publique - Hopitaux de Paris - Hopital Saint-Louis

    Paris, 75475

  • Assistance Publique - Hopitaux de Paris - La Pitié Salpétrière

    Paris, 75651

  • Centre Jean Godinot

    Reims, 51056

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Belgium6 sites

  • A.Z. St. Jan

    Bruges, 8000

  • Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

    Brussels, 1000

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • Universitair Ziekenhuis Antwerpen

    Edegem, Antwerpen, 2650

  • Universitair Ziekenhuis Gent

    Ghent, 9000

  • U.Z. Leuven - Campus Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Netherlands3 sites

  • University Medical Center Groningen

    Groningen, 9713

  • Leiden University Medical Centre

    Leiden, 2300

  • Radboud University Medical Center Nijmegen

    Nijmegen, 6500

Other trials in Netherlands

Germany2 sites

  • Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern

    Munich, DE 81377

  • Universitaetsklinikum Wuerzburg

    Würzburg, DE 97080

Other trials in Germany

Italy2 sites

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

  • Azienda Ospedaliera Universitaria "Federico II"

    Naples, 80131

Other trials in Italy

United Kingdom2 sites

  • NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital

    Glasgow, G12 0YN

  • Royal Marsden Hospital - Sutton, Surrey

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Denmark1 site

  • Odense University Hospital

    Odense, 5000

Other trials in Denmark

Poland1 site

  • Maria Sklodowska-Curie Memorial Cancer Centre

    Warsaw, PL 02 781

Other trials in Poland

Spain1 site

  • Hospital General Vall D'Hebron

    Barcelona, ES 08035

Other trials in Spain

About this study

Official title: 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.

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.

Read more

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.

Being tested
Nintedanib, Placebo
Keywords
Thyroid Cancer, Medullary thyroid cancer (MTC), Differentiated thyroid cancer (DTC)
Medical subject headings
Carcinoma, Medullary, Thyroid Neoplasms

What participants receive

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

  • NintedanibDrug

    Also called BIBF1120

    Nintedanib should be administered orally at a dose of 200 mg twice daily.

  • PlaceboDrug

Study groups in NCT01788982
Study groupRoleWhat they receive
NintedanibExperimentalNintedanib should be administered orally at a dose of 200 mg twice daily.
Receives: Drug: Nintedanib
PlaceboPlacebo comparatorPlacebo should be administered orally at a dose of 200 mg twice daily. Cross-over to nintedanib is allowed after progression.
Receives: Drug: Nintedanib; Drug: Placebo

What is being measured

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

  1. Progression free survival (PFS)

    This study will use RECIST 1.1 to measure PFS

    Measured: 2,5 years from FPI

Secondary outcomes (4)

  1. Occurence of Adverse Events

    This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

    Measured: 2,5 years from FPI

  2. Response Rate

    This study will use RECIST 1.1 to measure RR

    Measured: 2,5 years from FPI

  3. Duration of response

    This study will use RECIST 1.1 to measure duration of response

    Measured: 2,5 years form FPI

  4. Exploration of the molecular mechanisms of action of drug

    The biomarker study in this protocol is exploratory in nature.Spearman Correlation Coefficient will be computed to quantify the relationship between biomarkers and between biomarkers and clinical parameters (e.g. age). Fisher's exact test or Wilcoxon rank sum test will be used to assess the significance of these relationships.

    Measured: 3 years from FPI

Timeline

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

  1. First posted11 Feb 2013 (estimated)
  2. Study startMay 2014
  3. Primary completion28 Aug 2019
  4. Study completion28 Aug 2019

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01788982
Sponsor's protocol ID
EORTC-1209
Other IDs
2012-004295-19
Status last verified
Jul 2020
First submitted
8 Feb 2013
Last updated
31 Jul 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Leboulleux S, Kapiteijn E, Litiere S, Schoffski P, Godbert Y, Rodien P, Jarzab B, Salvatore D, Zanetta S, Capdevila J, Bastholt L, De La Fouchardiere C, Lalami Y, Bardet S, Cornelis F, Dedecjus M, Links T, Sents W, Schlumberger M, Locati DL, Newbold K. Safety and efficacy of nintedanib as second-line therapy for patients with differentiated or medullary thyroid cancer progressing after first-line therapy. A randomized phase II study of the EORTC Endocrine Task Force (protocol 1209-EnTF). Front Endocrinol (Lausanne). 2024 Jun 27;15:1403687. doi: 10.3389/fendo.2024.1403687. eCollection 2024.

    PubMed 39015176

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nintedanib in people with Medullary Thyroid Cancer (MTC) and Differentiated Thyroid Cancer (DTC), run by European Organisation for Research and Treatment of Cancer - EORTC at 27 sites in 9 countries.

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 41 inclusion and 0 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 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France, Belgium, Netherlands, Germany, Italy and 4 more countries. 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. Some participants in this study may receive a placebo. 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?

Progression free survival (PFS) (time frame: 2,5 years from FPI). 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 NCT01788982, which also lists 1 linked publication.

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 31 Jul 2020.

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