A Phase II, single arm Study of avelumab in combination with Axitinib in Patients with unresectable/metastatic Gastrointestinal Stromal Tumor after failure of standard therapy - AXAGIST

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy2 sites in 2 countries58 target enrollmentJanuary 11, 2025

DrugsInlyta 1 mg film-coated tablets Bavencio 20 mg/mL concentrate for solution for infusion Recombinant human monoclonal IgG1 antibody against programmed death ligand-1 Inlyta 5 mg film-coated tablets MSB 0010718C MSB0010718C

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Enrollment: 58
Locations: 2
Primary Endpoint: Rate of Participants Achieving 3-Month Progression-Free Survival (PFSR) [Rate of participants who are progression-free at 3 months after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Progression-free survival (PFS) is defined as the time from treatment initiation until documented disease progression or death (by any cause, in the absence of progression)].
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To assess anti-tumor activity of avelumab in combination with axitinib in patients with unresectable/metastatic GIST after progression on second or third line treatment (after failure on at least of imatinib and sunitinib) in terms of progression-free survival (PFS)

Registry

euclinicaltrials.eu

Start Date

January 11, 2025

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Responsible Party

Principal Investigator

główny badacz

Scientific

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Eligibility Criteria

Inclusion Criteria

•Signed written informed consent.
•Adequate hepatic function defined by - total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), - an AST level ≤ 2.5 × ULN, and an ALT level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN.
•Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min on the basis of the Cockroft- Gault glomerular filtration rate estimation: (140-age) x (weight in kg) x (0,85 if female)/72x(serum creatinine in mg/dl)
•No clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), Uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg , unstable angina, congestive heart failure (≥2 New York Heart Association Classification medication) serious cardiac arrhythmia. All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject’s tolerance of trial treatment;
•Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
•Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) >1.5 or an activated partial thromboplastin time (aPTT) >1.5 x ULN within 7 days prior to first study treatment. Note: Patients receiving full dose oral or parenteral anticoagulants may be included in the study as long as anticoagulant dosing has been stable for at least 2 weeks prior to study entry and the appropriate coagulation monitoring tests are within local therapeutic limits;
•Effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the study drugs on the developing human fetus are unknown. Thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods e.g. implants, injectables, combined oral contraceptives in combination with a barrier method, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner;)
•Availability of representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks.
•Male or female subjects aged ≥ 18 years.
•Histologically proven locally advanced or metastatic GIST. C-Kit (CD117) positive tumors detected by immunohistochemistry

Exclusion Criteria

•Concurrent anticancer treatment within 14 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin); major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy); use of hormonal agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment.
•Significant acute or chronic infections including, among others: positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
•Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study.
•Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test and positive HCV RNA test at screening
•Active tuberculosis
•Severe infection within 2 weeks prior initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteriemia or severe pneumonia
•Brain or leptomeningeal metastases, history of intracranial hemorrhage
•Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study
•Known alcohol or drug abuse
•Inability or unwillingness to swallow pills

Outcomes

Primary Outcomes

Rate of Participants Achieving 3-Month Progression-Free Survival (PFSR) [Rate of participants who are progression-free at 3 months after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Progression-free survival (PFS) is defined as the time from treatment initiation until documented disease progression or death (by any cause, in the absence of progression)].

Secondary Outcomes

Progression free survival (PFS) [time from treatment initiation to date of first documentation of progression of disease assessed by the Investigator (by RECIST version 1.1) or death due to any cause]
Overall survival (OS) [time from the date of treatment initiation until the date of death from any cause]
1-year overall survival (OS) rate [proportion of patients that survive more than 1 year]
Overall response rate (ORR) [ORR is defined as the proportion of patients with objective response [confirmed complete (CR) or partial response (PR) according to RECIST Version 1.1]
Duration of response (DoR) [the time from documentation of tumor response to disease progression]
Disease control rate (DCR) [patients whose best response was CR or PR or Stable Disease (SD)]
Adverse events (graded according to the Common Toxicity Criteria for the Adverse Events, CTC-AE, version 4.0) assessed every 4 weeks
Relationship between PDL-1 expression and measures of efficacy, including ORR, DCR, PFS and OS
Relationship between biomarkers in blood/tissue and efficacy, including ORR, DCR, PFS and OS