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Gastro Intestinal Stromal TumourPhase 2LENVAGISTNCT04193553

Multicentre Placebo-controlled Double-blinded Phase II Study of Lenvatinib Efficacy in Patients With Locally Advanced or Metastatic GIST (Gastrointestinal Stromal Tumor) After Imatinib/Sunitinib Failure

A Phase 2 study testing Lenvatinib in people with Gastro Intestinal Stromal Tumour, run by Centre Leon Berard at 14 sites in France.

Completed

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

Official record
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Trial summary

The primary objective is to compare the efficacy of lenvatinib plus Best Supportive Care versus Placebo plus Best Supportive Care in the treatment of patients with advanced GIST, after failure of imatinib and sunitinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastro Intestinal Stromal Tumour
What is being tested?
Lenvatinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
77 participants
Where
14 sitesFrance
Study dates
17 Jan 2020to 26 Apr 2024
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

  • I1. Male or female ≥ 18 years at the day of consenting to the study.
  • I2. Patient must have histologically confirmed diagnosis of GIST.
  • I3. Disease must be locally advanced or metastatic.
  • I4. Patient who failed (disease progression and/or intolerance) previously at least to imatinib and sunitinib.
  • Nota Bene: patients with more than 2 previous anticancer treatments are eligible.
  • I5. Patient must have evidence of measurable disease as per the RECIST version 1.1 (Appendix 2).
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  • I6. Patient must have documented disease progression. I7. ECOG performance status 0, 1 or 2 (Appendix 3).
  • I8. Patient must have normal organ and bone marrow function as defined below:
  • Hematologic
  • Absolute neutrophil count (ANC) ≥ 1.5 Gi/L
  • Haemoglobin ≥ 9 g/dl (5.6 mmol/l) (subjects may not have had a transfusion within 7 days of screening assessment)
  • Platelets ≥ 100 Gi/l
  • Coagulation panel
  • Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN)
  • Partial thromboplastin time (PTT) ≤ 1.2 X ULN Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.
  • Hepatic
  • Total bilirubin ≤ 1.5 X ULN
  • AST and ALT ≤ 2.5 X ULN
  • Renal
  • Serum creatinine ≤ 1.5 mg/dl (133 µmol/l) Or, if greater than 1.5 mg/dl: calculated creatinine clearance ≥ 50 ml/min
  • Urine Protein to Creatinine ratio (UPC) < 1; If UPC > 1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value <1g.
  • I9. Patient and his/her partner using an effective contraception as defined in Appendix 1.
  • I10. Patient able to understand and willingness for follow-up visits. I11. Patient covered by a medical insurance. I12. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to any study-specific procedure.

Who cannot join

  • E1. Patient with a documented mutation in PDGFRA exon 18 (D842V substitution).
  • E2. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesions with risk of bleeding
  • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
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  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
  • Malabsorption syndrome
  • Major resection of the stomach or small bowel.
  • E3. Any active/uncontrolled infection, including known infection with HIV, Hepatitis B or Hepatitis C.
  • E4. Corrected QT interval (QTc) > 480 msecs using Bazett's formula
  • E5. History of any one or more of the following cardiovascular conditions within the past 6 months prior to the first dose of study drug:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) classification.
  • E6. Poorly controlled arterial hypertension (Systolic blood pressure: 150mmHg / Diastolic blood pressure: 90mmHg).
  • Note: 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).
  • E7. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
  • E8. Evidence of active bleeding or bleeding diathesis. E9. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
  • E10. Clinically significant haemoptysis within 8 weeks of first dose of study drug.
  • E11. Any serious and/or unstable pre-existing medical, psychiatric, or other condition (geographic, social…) that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • E12. Unable or unwilling to discontinue use of prohibited medications list in Section 6.3 for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
  • E13. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.
  • E14. Inability to swallow E15. Any contraindication to Lenvima®, according to its Summary of Product Characteristics E16. History of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition of lenvatinib E17. 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.
  • E18. Pregnant or breastfeeding women. Women of childbearing potential (Appendix 1) 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 Note: Female if applicable, subjects should discontinue breast-feeding prior to the first dose of study drug and should refrain from breastfeeding throughout the treatment period and for 14 days following the last dose of study drug.
  • E19. Patient under tutorship or curatorship.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

France14 sites

  • Institut Bergonié

    Bordeaux, Gironde, 33076

  • Centre Georges-François Leclerc

    Dijon, Bourgogne-Franche-Comté, 21079

  • Centre Oscar LAMBRET

    Lille, Hauts-de-France, 59020

  • Centre Léon Bérard

    Lyon, Rhône, 69373

  • Hopital de La Timone

    Marseille, Bouches Du Rhône, 13385

  • Institut Paoli Calmette

    Marseille, Bouches-du-Rhône, 13273

  • Centre Antoine LACASSAGNE

    Nice, Alpes-Maritimes, 06189

  • CHU Poitiers

    Poitiers, Vienne, 86021

  • CHU de Reims

    Reims, Marne, 51000

  • Centre Eugène Marquis

    Rennes, Ille-et-Vilaine, 44229

  • ICO Centre René Gauducheau

    Saint-Herblain, Loire-Atlantique, 44805

  • Institut Universitaire du Cancer de Toulouse Oncopole

    Toulouse, Haute-Garonne, 31059

  • Institut de Cancérologie de Lorraine Alexis Vautrin

    Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511

  • Institut Gustave Roussy

    Villejuif, Val-de-Marne, 94805

Other trials in France

About this study

Official title: A Multicentre, Comparative, Placebo-controlled, Double-blinded, Phase II Study of the Efficacy of Lenvatinib in Patients With Locally Advanced or Metastatic GIST After Failure of Imatinib and Sunitinib

The primary objective is to compare the efficacy of lenvatinib plus Best Supportive Care versus Placebo plus Best Supportive Care in the treatment of patients with advanced GIST, after failure of imatinib and sunitinib.

Read the detailed description

Even though the prognosis of advanced GIST has been tremendously improved by the introduction of tyrosine kinase inhibitors, the vast majority of patients will develop secondary resistance to these agents.

The therapeutic options of patients with advanced GIST with resistance (or intolerance) to imatinib and sunitinib remain then very limited and prognosis of patients are very poor.

Nilotinib has an inferior activity in first line setting as compared to imatinib. Sorafenib has been evaluated in off-label and compassionate use studies with a median PFS close to 3 to 4 months, and a median overall survival close to 9 months with few prolonged tumor control and limited availability.

Regorafenib was tested in a phase II and a randomized phase III trial (GRID) in this setting , and provided a significant PFS advantage with no significant improvement in OS.

There are no recognized standard options in patients whose tumors progress after 3 or more TKIs. The recently updated guidelines from ESMO in 2014, included the reintroduction of imatinib in an attempt to control the progression of the sensitive cell clones, and on the basis of the results of the RIGHT study.

This is therefore a situation with a clear unmet medical need.

Lenvatinib is a broad spectrum TKI targeting oncogenes KIT and RET and receptor tyrosine kinases, PDGFRA, VEGFR 1-3 and FGFR 1-4. It has demonstrated activity in iodine resistant metastatic thyroid cancers. Whether lenvatinib would be a useful agent in patients with GIST is not known but there is a rationale to investigate its activity in patients with advanced GIST.

In the present study, we propose to analyze the antitumor activity of lenvatinib in patients with GIST failing to at least imatinib and sunitinib in a randomized setting, vs placebo.

Being tested
Lenvatinib, Placebo, Best supportive care
Keywords
Gastro Intestinal Stromal Tumour, Locally advanced or metastatic, Tyrosine kinase inhibitors
Medical subject headings
Neoplasm Metastasis

What participants receive

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

  • LenvatinibDrug

    Lenvatinib will be administered continuously but patient's follow-up visits will be scheduled monthly.

    The starting dose of study treatment is 24mg, once daily, at the same time. Recommendations for dose reductions will be respected according to BI Lenvatinib.

    If a patient misses a dose, and it cannot be taken within 12 hours, then that dose should be skipped and the next dose should be taken at the usual time of administration.

    Study treatments will be continued until a treatment discontinuation criteria is met.

  • PlaceboDrug

    Placebo will be administered continuously but patient's follow-up visits will be scheduled monthly.

    The starting dose of study treatment is 24mg, once daily, at the same time. Recommendations for placebo dose reductions are the same as for Lenvatinib. If a patient misses a dose, and it cannot be taken within 12 hours, then that dose should be skipped and the next dose should be taken at the usual time of administration.

    Study treatments will be continued until a treatment discontinuation criteria is met.

    In case disease progression, patients in control arm could switch in the Lenvatinib + BSC arm.

  • Best supportive careOther

    At any time during the study, patients should receive best supportive care. Best Supportive care as medically indicated for the patient's well-being may be prescribed at the investigator's discretion. Based on the patient's condition, it may consist (but not limited) of analgesics, antibiotics, steroids, blood transfusion, antiemetics, antidepressants/anxiolytics, nutritional counselling, psychological support, palliative radiotherapy…

Study groups in NCT04193553
Study groupRoleWhat they receive
Lenvatinib + Best Supportive CareExperimentalNot described
Receives: Drug: Lenvatinib; Other: Best supportive care
Placebo + Best Supportive CarePlacebo comparatorNot described
Receives: Drug: Placebo; Other: Best supportive care

What is being measured

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

  1. Progression-Free Survival (PFS)

    PFS, defined as the time from the date of randomisation to the date of the first documented radiological progression (RECIST 1.1) or death due to any cause.

    PFS will be estimated using the Kaplan-Meier method and will be described in terms of median PFS per arm, and hazard ratio for progression between the 2 arms. Associated 2-sided 95% CI for the estimates will be provided.

    Measured: Up to 30 months

Secondary outcomes (6)

  1. Overall Survival (OS)

    OS, is defined as the time from the date of randomisation until the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

    Measured: Up to 30 months

  2. Objective Response Rate (ORR) for patient in the blinded part of the study

    ORR, is the proportion of patients with a Complete Response or Partial Response as Best Overall Response.

    Measured: Up to 30 months

  3. Best Overall Response (BOR) for patient in the blinded part of the study

    BOR, is described as the proportion of patients with a best overall response of Complete Response, Partial Response, Stable Disease or Progressive Disease.

    Measured: Up to 30 months

  4. Quality of Life (QoL) for patient in the blinded part of the study

    QoL, will be assessed using the EORTC QLQ-C30. Scores will be calculated at each time point according to the scoring manuals. Descriptive statistics will be used to evaluate baseline scores and evolution of scores from baseline to each time point. Data will be compared between arms using the Student's t-test.

    Measured: Up to 30 months

  5. Patient's tolerance to treatment

    The safety will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. Adverse events will be coded according to the MedDRA®.

    Measured: Up to 30 months

  6. Progression-Free Survival (PFS) In patients from the placebo arm who switched into the active treatment group

    OS, is defined as the time from the date of randomisation until the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

    Measured: Up to 30 months

Timeline

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

  1. First posted10 Dec 2019
  2. Study start17 Jan 2020
  3. Primary completion30 Jan 2024
  4. Study completion26 Apr 2024

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
Double blind
Who is masked
Participant, Investigator
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04193553
Sponsor's protocol ID
ET18-291 - LENVAGIST
Acronym
LENVAGIST
Status last verified
Apr 2024
First submitted
5 Dec 2019
Last updated
18 Jun 2024
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 in people with Gastro Intestinal Stromal Tumour, 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 23 inclusion and 29 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 18 Jun 2024. 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. 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: Up to 30 months). 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 NCT04193553.

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 18 Jun 2024.

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