Metastatic Renal Cell CarcinomaPhase 2NivoMetNCT06884683
Nivolumab Plus Metformin in Metastatic Renal Cell Carcinoma
A Phase 2 study testing Metformin in people with Metastatic Renal Cell Carcinoma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 2 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Renal Cell Carcinoma
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesItaly
- Study dates
- 17 Sep 2020to 13 Sep 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- 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.
- 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.
Who cannot join
- 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
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- 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
- Other malignancy with a previous diagnosis within 5 years (with the exclusions of NMIBC, CIN).
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Phase II Study of Nivolumab Combined With Metformin in Pretreated Metastatic Renal Cell Carcinoma (mRCC) Patients. NivoMet TWINS-GU002 Study
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
- Being tested
- Metformin
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Nivolumab
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®
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
9-months PFS rate
The percentage of patients without disease progression after 9 months from the start of therapy
Measured: 9 months after the last enrolled patient
Secondary outcomes (4)
ORR
objective response rate (percentage of patients with complete or partial response
Measured: the ORR analysis will be performed after 12 months from the last patient enrolled
median PFS
median time of survival without disease progression
Measured: the PFS analysis will be performed after 12 months from the last patient enrolled
median OS
median time of overall survival
Measured: the OS analysis will be performed after 12 months from the last patient enrolled
Adverse Events
description and rate of treatment-related adverse events
Measured: AEs will be collected until 3 months from the discontinuation of the experimental therapy by the last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2025
- Study start17 Sep 2020
- Primary completion13 Sep 2023
- Study completion13 Sep 2023
Why it stopped: slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, TORTORA GIAMPAOLO, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Investigators
- Giampaolo Tortora, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06884683
- Sponsor's protocol ID
- 3209
- Acronym
- NivoMet
- Status last verified
- Mar 2025
- First submitted
- 14 Mar 2023
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Nivolumab Combined With Metformin in Pretreated Metastatic Renal Cell Carcinoma (mRCC) Patients. NivoMet TWINS-GU002 Study
- ClinicalTrials.gov ID
- NCT06884683
- Acronym / sponsor ID
- NivoMet / 3209
- Conditions
- Metastatic Renal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow enrollment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 17 Sep 2020 (actual)
- Primary completion
- 13 Sep 2023 (actual)
- Study completion
- 13 Sep 2023 (actual)
- First posted
- 19 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| experimental | Experimental | Drug: Metforminnivolumab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: NivolumabDrug: 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® | Drug | experimental |
Primary outcome
9-months PFS rate
Time frame: 9 months after the last enrolled patient
The percentage of patients without disease progression after 9 months from the start of therapy
4 secondary outcomes
ORR
Time frame: the ORR analysis will be performed after 12 months from the last patient enrolled
median PFS
Time frame: the PFS analysis will be performed after 12 months from the last patient enrolled
median OS
Time frame: the OS analysis will be performed after 12 months from the last patient enrolled
Adverse Events
Time frame: AEs will be collected until 3 months from the discontinuation of the experimental therapy by the last patient enrolled
Results and safety
The study was stopped early (reason given: slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giampaolo Tortora principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Metastatic Renal Cell Carcinoma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
9-months PFS rate (time frame: 9 months after the last enrolled patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025; AzTrials last refreshed its copy on 7 Nov 2026.