Study that evaluating the efficacy of lenvatinib in patients with locally advanced GIST after failure of imatinib and sunitinib

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Leon Berard

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Mar 2020 → 12 Mar 2025

Decision date (initial)

2024-08-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Eisai Limited ORG-100000323

External identifiers

EU CT number

2024-513984-22-00

EudraCT number

2018-004332-30

ClinicalTrials.gov

NCT04193553

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective is to compare the antitumor efficacy of lenvatinib versus placebo in patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib.

Secondary objectives 2

1. Secondary objectives of the blinded part of the study are to determine in both arms: • The Overall Survival (OS) • The Objective Response Rate (ORR)* • The Best Overall Response (BOR)* • The quality of Life (EORTC QLQ-C30) • The tolerance profile
2. In patients from the placebo arm who switched into the active treatment group, the following additional objectives will be studied from lenvatinib initiation:  The Progression-Free Survival (PFS)*  The Objective Response Rate (ORR)*  The Best Overall Response (BOR)*  The quality of Life (EORTC QLQ-C30)  The tolerance profile

Conditions and MedDRA coding

Patients with metastatic GIST

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. I1. Male or female ≥ 18 years at the day of consenting to the study
2. I2. Patient must have histologically confirmed diagnosis of GIST
3. I3. Disease must be locally advanced or metastatic
4. I4. Patient who failed (disease progression and/or intolerance) previously at least to imatinib and sunitinib
5. Nota Bene: for patients in 3rd line treatment, it is the investigator’s responsibility to determine on a case by case basis whether the best therapeutic option is to participate in this study or to receive regorafenib in its indication for use.
6. I5. Patient must have evidence of measurable disease as per the RECIST version 1.1 (Appendix 2)
7. I6. Patient must have documented disease progression
8. I7. ECOG performance status 0, 1 or 2 (Appendix 3)
9. 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.
10. I9. Patient and his/her partner using an effective contraception as defined in App. 1
11. I10. Patient able to understand and willingness for follow-up visits
12. I11. Patient covered by a medical insurance
13. 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

Exclusion criteria 19

1. E1. Patient with a documented mutation in PDGFRA exon 18 (D842V substitution)
2. 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  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
3. E3. Any active/uncontrolled infection, including known infection with HIV, Hepatitis B or Hepatitis C
4. E4. Corrected QT interval (QTc) > 480 msecs using Bazett's formula
5. 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
6. E6. Hypertension non contrôlée (Pression artérielle systolique : 150mmHg / Pression artérielle diastolique : 90mmHg). Note: Les patients ayant une pression artérielle élevée peuvent être inclus si l'hypertension est bien contrôlée avec un traitement antihypertenseur donnée à une dose stable durant au moins 1 semaine avant le début du traitement
7. 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).
8. E8. Evidence of active bleeding or bleeding diathesis
9. E9. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
10. E10.Clinically significant haemoptysis within 8 weeks of first dose of study drug.
11. 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.
12. 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.
13. E13.Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.
14. E14.Inability to swallow
15. E15.Toute contre-indication au Lenvima®, selon le Résumé des Caractéristiques du Produit
16. E16.History of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition of lenvatinib
17. 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
18. 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
19. E19.Patient under tutorship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the Progression-Free Survival (PFS)

Secondary endpoints 5

1. Overall survival is defined as the time from the date of randomisation until the date of death due to any cause.
2. Objective Response Rate (ORR) is the proportion of patients with a Complete Response or Partial Response as Best Overall Response.
3. Best Overall Response (BOR) is described as the proportion of patients with a best overall response of Complete Response.
4. The patient's Quality of Life will be assessed using the EORTC QLQ-C30.
5. The tolerance profile will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTC v5.0) grade.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

Pr LE CESNE Axel

Public contact point

Organisation

Centre Leon Berard

Contact name

Clinical Operations Manager

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications