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 (LENVAGIST)
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ClinicalTrials.gov Identifier: NCT04193553 |
Recruitment Status :
Recruiting
First Posted : December 10, 2019
Last Update Posted : March 29, 2023
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Tracking Information | |||||
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First Submitted Date ICMJE | December 5, 2019 | ||||
First Posted Date ICMJE | December 10, 2019 | ||||
Last Update Posted Date | March 29, 2023 | ||||
Actual Study Start Date ICMJE | January 17, 2020 | ||||
Estimated Primary Completion Date | September 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Progression-Free Survival (PFS) [ Time Frame: Up to 30 months ] 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.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||
Brief Title ICMJE | 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 | ||||
Official Title ICMJE | 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 | ||||
Brief 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. | ||||
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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Gastro Intestinal Stromal Tumour | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
74 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | September 2024 | ||||
Estimated Primary Completion Date | September 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria: 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). 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:
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. Exclusion Criteria: 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:
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:
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. |
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04193553 | ||||
Other Study ID Numbers ICMJE | ET18-291 - LENVAGIST | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | Centre Leon Berard | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Centre Leon Berard | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Centre Leon Berard | ||||
Verification Date | March 2023 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |