- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04258956
A Study of Avelumab In Combination With Axitinib in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumor After Failure of Standard Therapy (AXAGIST)
February 5, 2020 updated by: Maria Sklodowska-Curie National Research Institute of Oncology
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
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)
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
58
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Elzbieta Bylina, MSc
- Phone Number: 00 48 22 546 21 03
- Email: elzbieta.bylina@coi.pl
Study Contact Backup
- Name: Katarzyna Kozak, MD
- Phone Number: 00 48 22 564 21 72
- Email: katarzyna.kozak@coi.pl
Study Locations
-
-
-
Warsaw, Poland, 02-781
- Recruiting
- Maria Sklodowska-Curie National Research Institue of Oncology
-
Contact:
- Elzbieta Bylina, MSc
- Phone Number: 0048 22546 21 03
- Email: elzbieta.bylina@coi.pl
-
Contact:
- Katarzyna Kozak, MD
- Phone Number: 0048 225462172
- Email: katarzyna.kozak@coi.pl
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Signed written informed consent.
- Male or female subjects aged ≥ 18 years.
- Histologically proven locally advanced or metastatic GIST. C-Kit (CD117) positive tumors detected by immunohistochemistry
- Known mutational status KIT or PDGFRA.
- Documented disease progression (as per RECIST 1.1) within 3 months before study entry
- No more than 3 previous lines of treatment, which must include imatinib and sunitinib .
- Performance status ≤ 2 at trial entry and an estimated life expectancy of at least 3 months.
- Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1. Clinically and/or radiographically documented measurable disease within 21 days prior to registration
- Adequate hematological function defined by the following laboratory tests results, obtained within 14 days prior to initiation of study treatment
- - white blood cell (WBC) count ≥ 3 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
- - lymphocyte count ≥ 0.5 × 109/L,
- - platelet count ≥ 100 × 109/L,
- - hemoglobin ≥ 9 g/dL (patients may be transfused).
- 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.
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.
- Patients with PDGFRA D842V mutations are not eligible for this study.
- Previous treatment with anti-PD-1 or anti-PD-L1 antibodies, previous therapy with axitinib.
- Persisting toxicity related to prior therapy Grade > 1 CTCAE v 4.0,
- Major surgical procedure within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment; or minor surgical procedures, within 24 hours prior to the first study treatment;
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid. The use of inhaled corticosteroids for chronic obstructive pulmonary disease is allowed.
- History of abdominal fistula, grade 4 bowel obstruction or gastrointestinal perforation, intra-abdominal abscess within 6 months of enrollment;
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
- 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
- Pregnant or breastfeeding, or intending to become pregnant during the study. Woman of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
- Symptomatic brain metastases, history of intracranial hemorrhage
- Previous enrollment in this study
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: 12 weeks
|
12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
April 30, 2019
Primary Completion (ANTICIPATED)
April 30, 2021
Study Completion (ANTICIPATED)
April 30, 2023
Study Registration Dates
First Submitted
February 3, 2020
First Submitted That Met QC Criteria
February 5, 2020
First Posted (ACTUAL)
February 6, 2020
Study Record Updates
Last Update Posted (ACTUAL)
February 6, 2020
Last Update Submitted That Met QC Criteria
February 5, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Neoplasms, Connective Tissue
- Gastrointestinal Stromal Tumors
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Avelumab
- Axitinib
Other Study ID Numbers
- AXAGIST
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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