Metastatic Renal Cell Carcinoma
Conditions
Brief summary
Phase 2 single arm study that evaluated the addition of metformin to nivolumab in pre-treated metastatic renal cell carcinoma (mRCC) patients. Primary aim: to investigate the efficacy of the combination of nivolumab+metformin in mRCC patients previously treated with VEGFR-TKI Secondary aims: * to assess the activity, safety and efficacy of the experimental combination * to assess the quality of life of enrolled patients Enrolled patients will received: * nivolumab 240 mg e.v. every 14 day * metformin 500 mg orally twice a day continuously Patients will be trated untill disease progression, or unexpected toxicity, whichever comes first
Interventions
DRUGMetformin
Drug: metformin tablet 500 mg, 1 tablet twice a day (total dose 1000 mg daily), administered orally continuously \+ Biological: Nivolumab 240 mg via IV infusion every 14 days Other Names: Opdivo®
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent 2. Male and female aged 18 years and above 3. Histological confirmation of RCC with a clear cell component 4. Advanced or metastatic RCC 5. Measurable disease as defined by RECIST1.1criteria 6. Must have received at least one prior systemic treatment regimen in the advanced or metastatic setting, and must have evidence of progression on or after the last treatment regimen received 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 8. Adequate bone marrow and chemistry values defined as: 1. Hemoglobin ≥ 9.0 g/dL independent of transfusion 2. Platelet count ≥100.000/μL 3. Serum creatinine \< 1.5 x ULN or a calculated creatinine clearance ≥ 40 mL/min 4. Liver function: i. Serum bilirubin \< 1.5 x ULN (except for patients with documented Gilbert's disease) ii. AST or ALT \< 2.5 x ULN 9. Life expectancy of at least 6 months 10. WOCBP must use method(s) of contraception as determined to be acceptable by the principal investigator and sponsor during the study and for 23 weeks after last study drug administration. 11. Patients who are sexually active with WOCBP must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 31 weeks after last study drug administration.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study: 1. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection 2. Any active known or suspected autoimmune disease 3. Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease 4. Uncontrolled adrenal insufficiency 5. Evidence of active pneumonitis during screening, except for pulmonary fibrosis induced by prior thoracic irradiation 6. Dialitic patients 7. Diabetes mellitus 8. Any history of biguanide-based therapy within 1 year prior to enrollment 9. Current severe, uncontrolled systemic disease 10. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline 11. Other malignancy with a previous diagnosis within 5 years (with the exclusions of NMIBC, CIN). 12. Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 13. WOCBP who are pregnant or breastfeeding 14. Women with a positive pregnancy test at enrollment or prior to administration of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 9-months PFS rate | 9 months after the last enrolled patient | The percentage of patients without disease progression after 9 months from the start of therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | the ORR analysis will be performed after 12 months from the last patient enrolled | objective response rate (percentage of patients with complete or partial response |
| median PFS | the PFS analysis will be performed after 12 months from the last patient enrolled | median time of survival without disease progression |
| median OS | the OS analysis will be performed after 12 months from the last patient enrolled | median time of overall survival |
| Adverse Events | AEs will be collected until 3 months from the discontinuation of the experimental therapy by the last patient enrolled | description and rate of treatment-related adverse events |
Countries
Italy
Outcome results
None listed