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

NCT03013335 | Completed Phase 2 DMC

• 1 other identifier: UC-0160/1506 GETUG-AFU 26
• Study Type: interventional
• Target: 730
• Locations: 1 country
• Sites: 7

Brief 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 monotherapy.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Clear-cell; Nivolumab; Renal cell carcinoma; Immunotherapy

Outcome Measures

Primary Outcomes (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.

  5 years

Secondary Outcomes (9)

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

  5 years

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

  5 years

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

  5 years

• Percentage of patients who received immune modulating concomitant medication

  5 years

• Percentage of patients who received hormonal replacement therapy

  5 years

Study Arms (1)

Nivolumab

EXPERIMENTAL

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

Drug: Nivolumab

Interventions

Nivolumab DRUG

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

Nivolumab

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• UNICANCER: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli-Calmettes

Marseille, 13273 Cedex 9, France

Location

Centre Antoine Lacassagne

Nice, 06189 Cedex 2, France

Location

Institut de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, 54500, France

Location

Gustave Roussy Cancer Campus Grand Paris

Villejuif, 94800, France

Location

Related Publications (3)

• 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.

  PMID: 35977881 DERIVED

• 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.

  PMID: 33959132 DERIVED

• 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.

  PMID: 31194611 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bernard ESCUDIER

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

• Laurence ALBIGES

  Gustave Roussy, Cancer Campus, Grand Paris

  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: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: January 6, 2017
• Study Start: January 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 30, 2021
• Last Updated: October 6, 2021

Record last verified: 2021-10

Locations

FR (7)