Informations générales (source: ClinicalTrials.gov)
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) (LENVOS)
Interventional
Phase 2
Centre Leon Berard (Voir sur ClinicalTrials)
juillet 2019
janvier 2023
26 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Julien HADOUX | 16/04/2024 07:02:06 | Contacter | ||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - Nice - France | Danielle Benisvy, MD | Contact (sur clinicalTrials) | |||
| Centre Geogres François Leclerc - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| CHRU Besançon - Besançon - France | Fabien Calcagno, MD | Contact (sur clinicalTrials) | |||
| CHU Bordeaux - Hôpital Saint-André - 33075 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Hospices Civils de Lyon - Groupement Hospitalier Est - Bron - France | Françoise Borson-Chazot, MD | Contact (sur clinicalTrials) | |||
| Institut du Cancer Strasbourg (ICANS) - Strasbourg - France | Olivier Schneegans, MD | Contact (sur clinicalTrials) | |||
| Institut Jean Godinot - Reims - France | Jean-Christophe EYMARD, MD | Contact (sur clinicalTrials) | |||
| Institut Universitaire du Cancer de Toulouse - Oncopole - Toulouse - France | Slimane Zerdoud, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| APHP La Pitié Salpétrière - 75651 - Paris - France | Johanna Wassermann, Dr | Contact (sur clinicalTrials) | |||
| APHP Saint Louis - 75010 - Paris - France | Cécile CHOUGNET, Dr | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69008 - Lyon - France | DE LA FOUCHARDIERE Christelle, Dr | Contact (sur clinicalTrials) | |||
| CHU Angers - 49933 - Angers - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- 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,
- 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.
- 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,
- 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.