Nivolumab Plus Metformin in Metastatic Renal Cell Carcinoma

NCT06884683 | Terminated Phase 2

• 1 other identifier: 3209
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 9-months PFS rate

  The percentage of patients without disease progression after 9 months from the start of therapy

  9 months after the last enrolled patient

Secondary Outcomes (4)

• ORR

  the ORR analysis will be performed after 12 months from the last patient enrolled

• median PFS

  the PFS analysis will be performed after 12 months from the last patient enrolled

• median OS

  the OS analysis will be performed after 12 months from the last patient enrolled

• Adverse Events

  AEs will be collected until 3 months from the discontinuation of the experimental therapy by the last patient enrolled

Study Arms (1)

experimental

EXPERIMENTAL

nivolumab plus metformin Participants will receive nivolumab 240 mg e.v. every 14 days. Treatment will continue until progressive disease or discontinuation. Participants will receive metformin 500 mg orally twice a day. Treatment will continue until progressive disease or discontinuation.

Drug: Metformin

Interventions

Metformin DRUG

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®

Also known as: Nivolumab

experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Male and female aged 18 years and above
• Histological confirmation of RCC with a clear cell component
• Advanced or metastatic RCC
• Measurable disease as defined by RECIST1.1criteria
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Adequate bone marrow and chemistry values defined as:
• Hemoglobin ≥ 9.0 g/dL independent of transfusion
• Platelet count ≥100.000/μL
• Serum creatinine \< 1.5 x ULN or a calculated creatinine clearance ≥ 40 mL/min
• 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
• Life expectancy of at least 6 months
• 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.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from the study:
• 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
• Any active known or suspected autoimmune disease
• 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
• Uncontrolled adrenal insufficiency
• Evidence of active pneumonitis during screening, except for pulmonary fibrosis induced by prior thoracic irradiation
• Dialitic patients
• Diabetes mellitus
• Any history of biguanide-based therapy within 1 year prior to enrollment
• Current severe, uncontrolled systemic disease
• 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
• 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.
• WOCBP who are pregnant or breastfeeding
• Women with a positive pregnancy test at enrollment or prior to administration of study medication

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (2)

Giampaolo Tortora

Roma, Italy

Location

Francesca Primi

Viterbo, Italy

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Metformin; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Giampaolo Tortora

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director of Medical Oncology and Comprehensive Cancer Center

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: March 19, 2025
• Study Start: September 17, 2020
• Primary Completion: September 13, 2023
• Study Completion: September 13, 2023
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)