metastatic renal cell carcinoma MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: INLYTA - 1 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (ALU/ALU) 56 COMPRESSE
Product Name: Inlyta
Product Code: [Axitinib]
Pharmaceutical Form: Film-coated tablet
Current Spo
Sponsors
CONSORZIO ONCOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet the following criteria to be enrolled in this study. 1. Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype with primary tumor resected. 2. Availability of tumor tissue sample for biomarker analysis. 3. Male or female subjects aged = 18 years 4. At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. 5. Eastern Cooperative Oncology Group performance status 0 or 1. 6. Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before the start of treatment: I. Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L). II. Platelets = 100,000/mm3 (= 100 GI/L). III. Hemoglobin = 9 g/dL (= 90 g/L). IV. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Prior treatment with systemic therapy for advanced RCC 2. Prior adjuvant or neoadjuvant therapy 3. Bulky or symptomatic disease or hepatic metastases. 4. Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways 5. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis 6. Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low-grade prostate cancer (=pT2,N0; Gleason 6) with no plans for treatment intervention. 7. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the start of treatment. Systemic treatment with radionuclides within 6 weeks before the start of treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. 8. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before the start of treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of treatment. 9. Concomitant anticoagulation at therapeutic doses with oral anticoagulants 10. In past 6 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack. 11. Chronic treatment with corticosteroids or other immunosuppressive agents . Subjects with brain metastases requiring systemic corticosteroid are not eligible. 12. The subject has uncontrolled, significant intercurrent or recent illness 13. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 3 months before the start of treatment. Complete wound healing from major surgery must have occurred 1 month before the start of treatment and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before the start of treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. 14. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month before the start of treatment 15. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines. 16. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 17. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 18. History of substance abuse or medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results. 19. Illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the activity of the axitinib discontinuation in patients who received a previous induction with axitinib and avelumab.;Secondary Objective: •To evaluate the efficacy of the combination in terms of the control of the disease •To evaluate the efficacy of the combination in terms of the overall survival. •To evaluate the safety of the combination and of the discontinuation. •To evaluate the quality of life in patients who receive the combination and discontinue the tyrosine kinase inhibitor;Primary end point(s): To evaluate the rate of patients free of progression at week 8 from axitinib discontinuation and avelumab maintenance after 36 weeks of induction treatment with the combination of avelumab and axitinib.;Timepoint(s) of evaluation of this end point: 44 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression free survival in the overall population • Overall response rate in the overall population • Disease control rate in the overall population • Safety of the combination and of the avelumab alone after the combination. • To evaluate the Health-Related Quality Of Life (HRQOL) according to FKIS-19 questionnaire and Health status/utility (EQ-5D-5L) test. • To test the predictive role of the immunohistochemistry expression of PBRM1, PD-L1, CD31 and immune infiltration CD8+. • To evaluate the changes citokines evaluated at baseline, after 8 weeks of therapy and at tumor progression.;Timepoint(s) of evaluation of this end point: - continuous -every 12 weeks during the treatment with avelumab plus axitinib. During the axitinib discontinuation every 8 weeks for the first six month and every 12 weeks thereafter - continuous -every 12 weeks during the treatment with avelumab plus axitinib. During the axitinib discontinuation every 8 weeks for the first six month and every 12 weeks thereafter - continuous -every 12 weeks during the treatment with avelumab plus axitinib. During the axitinib discontinuation every 8 weeks for the first six month and every 12 weeks thereafter - continuous - every 2 weeks - continuous - every 4 weeks - end of study - end of study | — |
Countries
Italy
Contacts
Public ContactArea Gastroenterologia e Oncologia
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Outcome results
None listed