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Metastatic Renal Cell CarcinomaPhase 2NIVORENNCT03013335

Nivolumab in Patients With Metastatic Renal Cell Carcinoma Who Have Progresses During or After Prior Systemic Anti-angiogenic Regimen

A Phase 2 study testing Nivolumab in people with Metastatic Renal Cell Carcinoma, run by UNICANCER at 7 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of this study is to evaluate the incidence of high-grade (i.e. Grade 3-4 and Grade 5 of CTCAE v4.0) adverse reactions of interest in patients with metastatic RCC who have progressed during or after receiving at least one prior systemic anti-angiogenic treatment and who are eligible for nivolumab… 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?
Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
730 participants
Where
7 sitesFrance
Study dates
Jan 2016to 30 Jun 2021
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

  • Adult men and women ≥18 years.
  • Patients with a histologically confirmed Renal Cell Carcinoma with a clear-cell component.
  • Patients with metastatic (AJCC stage IV) Renal Cell Carcinoma, with at least one measurable lesion by CT Scan or MRI according to RECIST 1.1 or with clinically apparent disease that can be reliably monitored by the investigator.
  • Patients having received at least one prior systemic anti-angiogenic treatment including but not limited to: sunitinib, sorafenib, pazopanib, axitinib, and bevacizumab, in the advanced or metastatic setting. Prior cytokine therapies (e.g. IL-2, IFN-α), vaccine therapy or treatment with cytotoxics are allowed. Patients intolerant to prior systemic anti-angiogenic treatment can also be eligible (except hypersensitivity to other monoclonal antibodies). A maximum of 25% of patients with more than 2 prior systemic treatments will be recruited per sites.
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  • Favorable, intermediate or poor risk group patients measured by the international metastatic renal cell carcinoma database consortium (IMDC) model.
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  • Patients with brain metastases will be eligible if they are: asymptomatic, without edema, not on corticosteroids, not be eligible for radiation therapy/surgery and not receiving active treatments.
  • Patients who have progressed following radiation therapy. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks prior to the first nivolumab administration.
  • Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 31 weeks (≈ 7 months) for males and 23 weeks (≈ 5 months) for females after the last dose of study drug. Azoospermic males and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements.
  • Women of childbearing potential must have a negative serum pregnancy test done within 24 hours prior to the first dosing.
  • Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose.
  • Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
  • Patients with social insurance coverage.

Who cannot join

  • Patients with any active autoimmune disease or a history of known autoimmune disease (Patients with type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are however eligible for this trial).
  • Patients with uncontrolled adrenal insufficiency.
  • Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
  • Patients having received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Patients having received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal (influenza) vaccinations within 4 weeks of the first dose of study drug.
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  • Patients receiving anti-cancer therapies must be discontinued at least 2 weeks prior to administration of study drug. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks before administration of study drug. All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 (NCI-CTCAE version 4) or baseline before administration of study drug.
  • Patients with other prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.
  • Patients with altered hematopoietic or organ function, as indicated by the following criteria (assessed within 14 days prior the first dosing):
  • White blood cell count <2000/µL
  • Polynuclear neutrophils <1.5 x 10⁹/L
  • Platelets <100 x 10⁹/L
  • Hemoglobin <8.0 g/mL
  • Alanine aminotransferase (ALAT)/ aspartate aminotransferase (ASAT) >3.0 x upper limit of normal (ULN) in the absence of liver metastases or >5 x ULN in the presence of liver metastases
  • Bilirubin >1.5 x ULN (except Gilbert Syndrome: <3.0 mg/dL)
  • Creatinine clearance ≤40 mL/min (measured or calculated by Cockcroft and Gault formula) or serum creatinine >2.0 x ULN
  • Patients with a history of hypersensitivity to other monoclonal antibodies or to the active or inactive excipients of study drug.
  • Known drug or alcohol abuse.
  • Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events.
  • History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
  • Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study.
  • Individuals deprived of liberty or placed under the authority of a tutor.
  • Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment and during the treatment period.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • Centre Francois Baclesse

    Caen, 14076

  • Centre Georges-Francois Leclerc

    Dijon, 21079

  • Centre Leon Berard

    Lyon, 69373

  • Institut Paoli-Calmettes

    Marseille, 13273 Cedex 9

  • Centre Antoine Lacassagne

    Nice, 06189 Cedex 2

  • Institut de Cancerologie de Lorraine

    Vandœuvre-lès-Nancy, 54500

  • Gustave Roussy Cancer Campus Grand Paris

    Villejuif, 94800

Other trials in France

About this study

Official title: A Phase II Safety Trial of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Who Have Progresses During or After Prior Systemic Anti-angiogenic Regimen

The primary objective of this study is to evaluate the incidence of high-grade (i.e. Grade 3-4 and Grade 5 of CTCAE v4.0) adverse reactions of interest in patients with metastatic RCC who have progressed during or after receiving at least one prior systemic anti-angiogenic treatment and who are eligible for nivolumab monotherapy.

Read the detailed description

The present study will be carried out in patients suffering from refractory metastatic Renal Cell Carcinoma. The overall study population consists of 450 adult patients.

In France, 10600 patients were diagnosed with kidney cancer in 2010. At the time of their diagnosis, approximately 30% of patients present with metastatic disease, with 90 to 95% of that metastatic disease being of the clear-cell histology.

The present study is a multicenter, open-label, non-controlled, phase II safety study in patients who are suffering from metastatic Renal Cell Carcinoma and who have progressed during or after one prior systemic anti-angiogenic treatment. Patients intolerant to prior systemic anti-angiogenic treatment can also be eligible.

The dose and schedule of nivolumab in this study will be 3 mg/kg every 2 weeks. Nivolumab will be administered every 2 weeks until death, disease progression, unacceptable toxicity or withdrawal of the informed consent. 450 patients should be included over a period of 1 year

Being tested
Nivolumab
Keywords
Clear-cell, Nivolumab, Renal cell carcinoma, Immunotherapy
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.

  • NivolumabDrug

    The dose and schedule of nivolumab in this study will be 3 mg/kg every 2 weeks. Infusion of nivolumab will be performed in 30 minutes (± 5 minutes).

    Nivolumab will be administered every 2 weeks until death, disease progression, unacceptable toxicity or withdrawal of the informed consent

Study groups in NCT03013335
Study groupRoleWhat they receive
NivolumabExperimentalThe dose and schedule of nivolumab in this study will be 3 mg/kg every 2 weeks. Infusion of nivolumab will be performed in 30 minutes (± 5 minutes). Nivolumab will be administered every 2 weeks until death, disease progression, unacceptable toxicity or withdrawal of the informed consent
Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence for high-grade (Grade3-4-5) adverse reactions of interest

    The primary endpoint of this study is the incidence for high-grade (CTCAE v4.0 Grade 3-4 and Grade 5) adverse reactions of interest (i.e. adverse event related to study treatment).

    The adverse reactions of interest are: skin, endocrinopathy, gastrointestinal, hepatic, renal, pulmonary, and hypersensitivity adverse events.

    Measured: 5 years

Secondary outcomes (9)

  1. Assessment of Overall Survival (OS) by Follow-up continued

    The efficacy data assessed by measuring the OS :

    OS is defined as the time from first dosing date to the date of death. A patient who has not died will be censored at last known date alive. OS will be followed continuously while patients are on the treatment and every 3 months via in-person or phone contact after patients discontinue the study drug.

    Measured: 5 years

  2. Number of patients with a Best Overall Response (BOR) by RECIST v1.1

    Measured: 5 years

  3. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Safety and tolerability will be measured by the incidence of all adverse events, serious adverse events, deaths and laboratory abnormalities. Adverse event assessments and laboratory tests will be performed at baseline, and continuously throughout the study at the beginning of each subsequent cycle.

    Measured: 5 years

  4. Percentage of patients who received immune modulating concomitant medication

    The percentage of patients who received immune modulating concomitant medication (e.g., corticosteroids, infliximab, cyclophosphamide, IVIG, mycophenolate mofetil), collected in a specific form.

    Measured: 5 years

  5. Percentage of patients who received hormonal replacement therapy

    The percentage of patients who received hormonal replacement therapy.

    Measured: 5 years

  6. Median time to resolution of adverse reactions of interest

    The median time to onset, median time to resolution (Grade 3-4) of adverse reactions of interest.

    Measured: 5 years

  7. Assessment of quality of life by questionnaire FACT-G

    Patient reported outcomes will be assessed by FACT-G

    Measured: 5 years

  8. Assessment of quality of life by questionnaire FKSI-19

    Patient reported outcomes will be assessed by FKSI-19.

    Measured: 5 years

  9. Assessment of quality of life by questionnaire EQ-5D

    Global health status will be assessed by EQ-5D instrument.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2017 (estimated)
  2. Study startJan 2016
  3. Primary completionJun 2018
  4. Study completion30 Jun 2021

Resources

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
730 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03013335
Sponsor's protocol ID
UC-0160/1506 GETUG-AFU 26
Acronym
NIVOREN
Status last verified
Oct 2021
First submitted
10 Nov 2016
Last updated
6 Oct 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Rassy E, Dalban C, Colomba E, Derosa L, Alves Costa Silva C, Negrier S, Chevreau C, Gravis G, Oudard S, Laguerre B, Barthelemy P, Goupil MG, Geoffrois L, Rolland F, Thiery-Vuillemin A, Joly F, Ladoire S, Tantot F, Escudier B, Albiges L. Efficacy and Safety of Concomitant Proton Pump Inhibitor and Nivolumab in Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study. Clin Genitourin Cancer. 2022 Oct;20(5):488-494. doi: 10.1016/j.clgc.2022.07.003. Epub 2022 Jul 10.

    PubMed 35977881

  • Billon E, Chanez B, Rochigneux P, Albiges L, Vicier C, Pignot G, Walz J, Chretien AS, Gravis G, Olive D. Soluble BTN2A1 Is a Potential Prognosis Biomarker in Pre-Treated Advanced Renal Cell Carcinoma. Front Immunol. 2021 Apr 20;12:670827. doi: 10.3389/fimmu.2021.670827. eCollection 2021.

    PubMed 33959132

  • Flippot R, Dalban C, Laguerre B, Borchiellini D, Gravis G, Negrier S, Chevreau C, Joly F, Geoffrois L, Ladoire S, Mahammedi H, Rolland F, Gross-Goupil M, Deluche E, Priou F, Laramas M, Barthelemy P, Narciso B, Houede N, Culine S, Oudard S, Chenot M, Tantot F, Chabaud S, Escudier B, Albiges L. Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study. J Clin Oncol. 2019 Aug 10;37(23):2008-2016. doi: 10.1200/JCO.18.02218. Epub 2019 Jun 13.

    PubMed 31194611

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab in people with Metastatic Renal Cell Carcinoma, run by UNICANCER at 7 sites in France.

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 13 inclusion and 23 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: finished, as of the sponsor's last update on 6 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence for high-grade (Grade3-4-5) adverse reactions of interest (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03013335, which also lists 3 linked publications.

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 6 Oct 2021.

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