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Thyroid Cancer MetastaticPhase 2LENVOSNCT03732495

Study of the Efficacy of Lenvatinib Combined With Denosumab in the Treatment of Patients With Predominant Bone Metastatic Radioiodine Refractory Differentiated Thyroid Carcinomas

A Phase 2 study testing Lenvatinib + Denosumab in people with Thyroid Cancer Metastatic, run by Centre Leon Berard at 14 sites in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study evaluates the combination of lenvatinib with denosumab in bone-predominant metastatic Radioiodine Refractory Differentiated Thyroid Carcinomas. All patients will receive this combination of treatments. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Cancer Metastatic
What is being tested?
Lenvatinib + Denosumab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
14 sitesFrance
Study dates
26 Jul 2019to 15 Jan 2023
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

  • Males or females of 18 years of age or older at the day of consenting to the study;
  • I2. Patients with follicular cell-derived thyroid (papillary, vesicular or and poorly differentiated);
  • Radioiodine-Refractory disease as defined by at least one of the following :
  • Presence of malignant/metastatic tissue that does not concentrate radioiodine (RAI),
  • Loss by the tumor tissue of the ability to concentrate RAI after previous evidence of RAI-avid disease,
  • Concentration of RAI in some lesions but not in others,
Show all 57Show fewer
  • Progression of metastatic disease despite significant concentration of RAI;
  • Predominant bone metastases (without threatening extra-bone metastasis)
  • Patient at risk of Skeletal-Related Event defined by the occurrence of at least one of the following event within 12 months prior to inclusion:
  • Skeletal-Related Event, including indication of loco regional procedure (i.e. radiation therapy, interventional radiology),
  • Progressive disease with measurable metastatic bone lesion(s) as per the RECIST1.1; Nota Bene: bone lesions with soft tissue involvement are considered as measurable.
  • Performance Status of the Eastern Cooperative Oncology Group (ECOG) ≤2;
  • Adequate organ function within 14 days prior to treatment start, defined as the following:
  • Neutrophils count ≥ 1.5 Gi/l
  • Hemoglobin ≥ 9.0 g/dl
  • Platelets count ≥ 100 Gi/l
  • Prothrombin Time (PT) ≤ 1.2 x ULN or International Normalized Ratio ≤ 1.5 Nota bene: Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the targeted anticoagulation.
  • Serum transaminases (ASAT and ALAT) ≤ 3.0 x upper limit of the normal (ULN) (5.0 x ULN in case of liver metastases)
  • Serum total bilirubin ≤ 2 x ULN
  • Creatinine clearance ≥ 30ml/min;
  • Absence of proteinuria Nota Bene: patients with proteinuria ≥1+ on dipstick urinalysis will have to undergo 24 hours urine collection. Subjects with urine protein ≥1g/24h will be ineligible;
  • Albumin-adjusted serum calcium ≥ 2.0 mmol/l (8.0mg/dl) and ≤ 2.9 mmol/l (11.5mg/dl)
  • Patient and his/her partner using 2 forms of effective contraception:
  • For women of child-bearing potential: at least 4 weeks prior to study entry, during the study participation and for at least 1 month post-lenvatinib and at least 5 months post-denosumab,
  • For men: at least 4 weeks prior to study entry and during the study participation;
  • Patient must be covered by a medical insurance;
  • Willingness and ability to comply with the study requirements;
  • Signed and dated informed consent indicating that the patient has been informed of all the aspects of the trial prior to enrolment.
  • Non-inclusion Criteria:
  • Histological diagnosis of the following DTC subtypes: medullar, anaplastic, lymphoma or sarcoma;
  • Prior history of malignancies other than study disease within the last 3 years, except locally curable disease with no sign of relapse;
  • Prior or current treatment with denosumab or any other bone-directed agent (including bisphosphonates), regardless of the indication;
  • Prior or current treatment with any tyrosine kinase inhibitor, including but not limited to lenvatinib and denosumab ;
  • Patient with imminent or confirmed Skeletal-Related Event as defined in the protocol;
  • Uncontrolled arterial hypertension (150mmHg/90mmHg) despite an optimal antihypertensive intervention; patients with high blood pressure can be enrolled provided that the hypertension is well controlled at a stable dose of antihypertensive therapy for at least 1 week prior to lenvatinib start;
  • Any condition leading to an increased risk of bleeding or hemorrhage;
  • Any other contraindication to lenvatinib and/or denosumab
  • Major surgery within 3 weeks prior to the first study drug administration or major surgery planned during the course of the study;
  • Unhealed lesion from dental or oral surgery;
  • Any dental or jaw condition that may lead or already led to osteonecrosis of the jaw or to oral surgery; Nota Bene: a consultation with a specialist must confirm that dental and oral cavity assessment allows starting a treatment with denosumab.
  • Any active infection, including known infection with HIV, Hepatitis B or Hepatitis C;
  • Patient participating to a clinical trial that can interfere with the primary outcome assessment or treatment with any investigational drug within 4 weeks prior to the start date of study drugs or planned during the study participation;
  • Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results;
  • Pregnant or breast feeding women. Women of childbearing potential* are required to have a negative serum pregnancy test within 72 hours prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test
  • : Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
  • ≥50 years old and naturally amenorrheic for ≥ 1 year
  • Permanent premature ovarian failure confirmed by a specialist gynecologist
  • Previous bilateral salpingo-oophrectomy
  • XY genotype, Turner's syndrome, or uterine agenesis Female patients who do not meet at least one of the above criteria are defined as women of childbearing potential.
  • Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of lenvatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection);
  • Patient with history or active gastrointestinal or non-gastrointestinal fistula;
  • Hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition of study drugs ;
  • History or active significant cardiovascular impairment : congestive heart failure greater than New York Heart Association class II, unstable angina, myocardial infarction, stroke, or cardiac arrhythmia associated with impairment within 6 months of the first dose of study drug;
  • Clinically significant electrocardiogram abnormality, including marked baseline prolonged QT/QTc interval (e.g., a repeated demonstration of a QTc interval > 500 msec);
  • Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results.
  • Patients using prohibited concomitant and/or concurrent medications.
  • Patient requiring tutorship or curatorship.

Who cannot join

None listed.

Trial locations and contacts

14 sites in 1 country.

Julien Gautier contact

0426556829 ext. +33

julien.gautier@lyon.unicancer.fr

14 sites in 1 country

France14 sites, 14 recruiting

  • CHU Angers

    Angers, 49933

    Frédéric ILLOUZ, MD

    Sandrine LABOUREAU-SOARES BARBOSA, MD

    Recruiting

  • CHRU Besançon

    Besançon

    Fabien Calcagno, MD, fcalcagno@chu-besancon.fr

    Fabien Calcagno, MD

    Recruiting

  • CHU Bordeaux - Hôpital Saint-André

    Bordeaux, 33075

    Laurence DIGUE, MD

    Alain RAVAUD, PhD

    Recruiting

  • Institut Bergonie

    Bordeaux

    GODBERT Yann, MD, y.godbert@bordeaux.unicancer.fr

    GODBERT Yann, MD

    Recruiting

  • Hospices Civils de Lyon - Groupement Hospitalier Est

    Bron

    Françoise Borson-Chazot, MD, francoise.borson-chazot@chu-lyon.fr

    Françoise Borson-Chazot, MD

    Recruiting

  • Centre Geogres François Leclerc

    Dijon, 21079

    Sylvie ZANETTA, MD

    Recruiting

  • Centre Léon Bérard

    Lyon, 69008

    DE LA FOUCHARDIERE Christelle, Dr, +33 4.78.78.27.51, christelle.delafouchardiere@lyon.unicancer.fr

    DE LA FOUCHARDIERE Christelle, MD

    Recruiting

  • Centre Antoine Lacassagne

    Nice

    Danielle Benisvy, MD, danielle.benisvy@nice.unicancer.fr

    Danielle Benisvy, MD

    Recruiting

  • APHP Saint Louis

    Paris, 75010

    Cécile CHOUGNET, Dr, 0142499411, cecile.chougnet@aphp.fr

    Recruiting

  • APHP La Pitié Salpétrière

    Paris, 75651

    Johanna Wassermann, Dr, 0142160518, johanna.wassermann@aphp.fr

    Recruiting

  • Institut Jean Godinot

    Reims

    Jean-Christophe EYMARD, MD

    Jean-Christophe EYMARD, MD

    Recruiting

  • Institut du Cancer Strasbourg (ICANS)

    Strasbourg

    Olivier Schneegans, MD, o.schneegans@icans.eu

    Olivier Schneegans, MD

    Recruiting

  • Institut Universitaire du Cancer de Toulouse - Oncopole

    Toulouse

    Slimane Zerdoud, MD, zerdoud.slimane@iuct-oncopole.fr

    Slimane Zerdoud, MD

    Recruiting

  • Institut Gustave Roussy

    Villejuif, 94805

    LEBOULLEUX Sophie, MD

    Recruiting

Other trials in France

About this study

Official title: A Prospective, Multicentre Phase II Study of the Efficacy of Lenvatinib Combined With Denosumab in the Treatment of Patients With Predominant Bone Metastatic Radioiodine Refractory Differentiated Thyroid Carcinomas (LENVOS)

This study evaluates the combination of lenvatinib with denosumab in bone-predominant metastatic Radioiodine Refractory Differentiated Thyroid Carcinomas. All patients will receive this combination of treatments.

Read the detailed description

Patients are usually considered for directed therapy (radiotherapy and/or surgery and/or thermo-ablation) in case of symptomatic lesions or at high risk of local complications. They also usually receive systemic bone-directed agents (bisphosphonate or denosumab), despite sparse available data in the context of differentiated thyroid carcinomas (DTC). As bone-directed agents have no antitumor activity, patients may require additional treatments. To date, only sorafenib and lenvatinib have been approved in the treatment of advanced Radioiodine Refractory Differentiated Thyroid Carcinomas (RR-DTC).

Lenvatinib demonstrated efficacy in RR-DTC compared to placebo. While other kinase inhibitors appeared to be less effective in controlling bone metastatic disease compared to other soft tissue sites, lenvatinib showed, in a small number of patients, significant decrease in bone tumors size.

Even if both study drugs are indicated in the treatment of patients suffering from RR-DTC with bone metastases, it is of essential importance to confirm that lenvatinib can provide clinical benefit and antitumor activity when combined with denosumab in this population.

Being tested
Lenvatinib + Denosumab

What participants receive

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

  • Lenvatinib + DenosumabDrug

    Lenvatinib and Denosumab will be used in the indication of their respective SmPCs.

    Study treatments will be divided in fictitious cycles of 28 days. Lenvatinib and Denosumab will be administered as per investigator's decision, based on the data from their SmPC, at starting doses of 24mg once daily and 120mg once every 4 weeks, respectively. Dose modification guidelines of their respective SmPCs will apply.

    Lenvatinib should be started the day after the inclusion. It will be taken every day at the same time, preferentially in the morning.

    As in routine practice, all patients will be supplemented with daily doses of at least 500mg Calcium and 400IU Vitamin D, unless hypercalcemia is present.

    Patients will be encouraged to maintain good oral hygiene during treatment with Denosumab.

    Study drugs will be continued until a treatment discontinuation criterion is met

Study groups in NCT03732495
Study groupRoleWhat they receive
Trial armExperimentalLenvatinib and Denosumab will be used in the indication of their respective SmPCs. Study treatments will be divided in fictitious cycles of 28 days. Lenvatinib and Denosumab will be administered as per investigator's decision, based on the data from their SmPC, at starting doses of 24mg once daily and 120mg once every 4 weeks, respectively. Dose modification guidelines of their respective SmPCs will apply. Lenvatinib should be started the day after the inclusion. It will be taken every day at the same time, preferentially in the morning. As in routine practice, all patients will be supplemented with daily doses of at least 500mg Calcium and 400IU Vitamin D, unless hypercalcemia is present. Patients will be encouraged to maintain good oral hygiene during treatment with Denosumab. Study drugs will be continued until a treatment discontinuation criterion is met.
Receives: Drug: Lenvatinib + Denosumab

What is being measured

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

  1. Determination of the efficacy of lenvatinib associated with denosumab in the treatment of patients with predominant bone metastases from Radioiodine-Refractory Differentiated Thyroid Carcinoma

    The 24-month Skeletal-Related Event-Free (24M-SREF) rate will be defined as the proportion of patients without occurrence of new bone metastatic lesions at 24 months

    Measured: 24 months

  2. Determination of the efficacy of lenvatinib associated with denosumab in the treatment of patients with predominant bone metastases from Radioiodine-Refractory Differentiated Thyroid Carcinoma

    The 24-month Skeletal-Related Event-Free (24M-SREF) rate will be defined as the proportion of patients without pathological bone fracture (either vertebral or non-vertebral) at 24 months

    Measured: 24 months

  3. Determination of the efficacy of lenvatinib associated with denosumab in the treatment of patients with predominant bone metastases from Radioiodine-Refractory Differentiated Thyroid Carcinoma

    The 24-month Skeletal-Related Event-Free (24M-SREF) rate will be defined as the proportion of patients without spinal cord compression at 24 months

    Measured: 24 months

  4. Determination of the efficacy of lenvatinib associated with denosumab in the treatment of patients with predominant bone metastases from Radioiodine-Refractory Differentiated Thyroid Carcinoma

    The 24-month Skeletal-Related Event-Free (24M-SREF) rate will be defined as the proportion of patients without bone-related orthopedic surgical intervention at 24 months

    Measured: 24 months

Secondary outcomes (8)

  1. Determination of the progression free survival

    Progression-Free Survival will be defined as the time from the date of inclusion to the date of first documented progression or death due to any cause

    Measured: 24 months

  2. Determination of the objective response rate

    Objective Response Rate will be defined as the proportion of patients with a best overall response of Complete Response or Partial Response during the study

    Measured: 24 months

  3. Determination of the time to the first local procedure

    Time to the first local procedure will be defined as the time from the date of inclusion to the date of any local procedure (external beam radiation therapy, thermoablation, cementoplasty…) aiming at relieving bone-related symptoms

    Measured: 24 months

  4. Determination of the time to treatment failure

    Time to Treatment Failure will be measured from the time of inclusion until discontinuation of treatment for any reason other than 'protocol deviation' or 'administrative problems', including SRE, clinical deterioration, treatment toxicity, and death.

    Measured: 24 months

  5. Determination of the analgesic consumption

    Analgesic consumption will be assessed and presented in morphine equivalent by 24 hours

    Measured: 24 months

  6. Determination of the Quality of life using European Organisation for Research and Treatment of Cancer (EORTC) questionnaire

    Using the EORTC QLQ-C30 (Quality of Life Questionnaire) - Scale range: 1 (better outcome) to 4 (worse outcome) for 28 variables and from 1 (better outcome) to 7 (worse outcome) for 2 variables

    Measured: 24 months

  7. Determination of the Quality of life using European Organisation for Research and Treatment of Cancer (EORTC) questionnaire

    Using the EORTC QLQ-BM22 (Bone Metastasis module) - Scale range 1 (better outcome) to 4 (worse outcome) for 22 items.

    Measured: 24 months

  8. Determination of the tolerance profile

    Tolerance profile will be described through the incidence and severity of drug-related adverse events (AE), AESI, SAE and deaths according to the last version of the NCI-CTC AE classification

    Measured: 24 months

Timeline

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

  1. First posted6 Nov 2018
  2. Study start26 Jul 2019
  3. Primary completion15 Dec 2022 (estimated)
  4. Study completion15 Jan 2023 (estimated)

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
Model description
Patients with predominant bone metastases from Radioiodine-Refractory Differentiated Thyroid Carcinoma (RR-DTC)
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03732495
Sponsor's protocol ID
ET17-191
Acronym
LENVOS
Status last verified
Oct 2021
First submitted
31 Oct 2018
Last updated
29 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib + Denosumab in people with Thyroid Cancer Metastatic, run by Centre Leon Berard at 14 sites in France.

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 57 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: status not confirmed, as of the sponsor's last update on 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in France. 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?

Results are not available in the source record.

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

Contact Julien Gautier (0426556829 ext. +33, julien.gautier@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the efficacy of lenvatinib associated with denosumab in the treatment of patients with predominant bone metastases from Radioiodine-Refractory Differentiated Thyroid Carcinoma (time frame: 24 months). The study lists 4 primary outcomes in all. 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 NCT03732495.

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 29 Mar 2022.

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