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

  • STATUS
    Recruiting
  • End date
    Jan 15, 2023
  • participants needed
    35
  • sponsor
    Centre Leon Berard
Updated on 23 April 2022

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.

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.

Details
Condition Thyroid Cancer Metastatic
Treatment Lenvatinib + Denosumab
Clinical Study IdentifierNCT03732495
SponsorCentre Leon Berard
Last Modified on23 April 2022

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note