A Phase 2 BIOmarker Driven Trial With Nivolumab and Ipilimumab or VEGFR tKi in Naïve Metastatic Kidney Cancer

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A Phase 2 BIOmarker Driven Trial With Nivolumab and Ipilimumab or VEGFR tKi in Naïve Metastatic Kidney Cancer

Condition: Clear Cell Metastatic Renal Cell Carcinoma

Intervention:

  • Drug: Nivolumab
  • Drug: Ipilimumab
  • Drug: Pazopanib
  • Drug: Sunitinib

Purpose: Disease and Stage: naïve metastatic kidney cancer. A multicenter, randomized, a Phase 2 BIOmarker driven trial with Nivolumab and Ipilimumab or VEGFR tKi in naïve metastatic Kidney cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02960906

Sponsor: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

Primary Outcome Measures:

  • Measure: ORR evaluation according to molecular groups (ccRCC1 to 4) and assigned treatment
  • Time Frame: 36 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free survival (PFS)
  • Time Frame: 36 months
  • Safety Issue:
  • Measure: Overall Survival
  • Time Frame: 36 months
  • Safety Issue:
  • Measure: Objective response rate at 22 weeks
  • Time Frame: at 22 weeks
  • Safety Issue:
  • Measure: Duration of treatment (DOT)
  • Time Frame: 36 months
  • Safety Issue:
  • Measure: Duration of response (DOR)
  • Time Frame: 36 months
  • Safety Issue:
  • Measure: Number of Participants With Treatment-Related Adverse Events
  • Time Frame: 36 months
  • Safety Issue:
  • Measure: Gene expression of immune population markers
  • Time Frame: at baseline at progression (36 months maximum)
  • Safety Issue:
  • Measure: Gene expression levels obtained from FFPE
  • Time Frame: at the end of the study (36 months)
  • Safety Issue:
  • Measure: Functional status of peripheral blood lymphocytes (PBL)
  • Time Frame: at baseline, at cycle 2 and at progression (36 months maximum)
  • Safety Issue:
  • Measure: Association between non-immune tissue and circulating biomarkers and outcomes
  • Time Frame: 36 months maximum
  • Safety Issue:

Estimated Enrollment: 150

Study Start Date: May 31, 2017

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Key Inclusion Criteria:

  • Histological confirmation of RCC with a clear-cell component. Patients with TFE3 or TFEB translocation proven by cytogenetic analysis or by fluorescence in situ hybridization (FISH) are eligible.
  • Metastatic (American Joint Committee on Cancer [AJCC] Stage IV) RCC
  • No prior systemic therapy for mRCC
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2
  • Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Frozen tumor samples (primary tumor and/or metastasis biopsies) must be available and received by the central laboratory (Cordelier Research Center) to determine molecular groups. (Note: fine needle aspiration [FNA] and bone metastases samples are not acceptable for submission).
  • Molecular group has to be determined prior to randomization.
  • Formalin-fixed, paraffin-embedded (FFPE) tumor tissue available for biomarker (gene expression and immunohistochemistry (IHC)) analysis.

Key Exclusion Criteria:

  • Any untreated CNS metastases. Patients with CNS metastases will be eligible if they are: asymptomatic, without significant oedema, not on corticosteroids, not eligible for radiation therapy/surgery or have already received radiation therapy.
  • Prior systemic treatment with vascular endothelial growth factor (VEGF) or VEGF receptor-targeted therapy (including, but not limited to, sunitinib, pazopanib, axitinib, tivozanib, and bevacizumab) except in an adjuvant setting with a free interval of more than 1 year.
  • Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type 1 diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
  • Any condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Uncontrolled adrenal insufficiency.
  • Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the Fridericia corrected QT (QTcF) interval defined as >450 msec for males and >470 msec for females, where QTcF = QT / 3√RR.
  • Poorly controlled hypertension (defined as systolic blood pressure (SBP) of >150 mmHg or diastolic blood pressure (DBP) of >90 mmHg), despite antihypertensive therapy.
  • History of any of the following cardiovascular conditions within 12 months of enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.
  • History of cerebrovascular accident including transient ischemic attack within the past 12 months.
  • History of deep vein thrombosis (DVT) unless adequately treated with low molecular weight heparin.
  • History of pulmonary embolism within the past 6 months unless stable, asymptomatic, and treated with low molecular weight heparin for at least 6 weeks.
  • Known history of COPD (of any stage).
  • Known history of uveitis or complaint of double vision.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
  • Serious, non-healing wound or ulcer.
  • Evidence of active bleeding or bleeding susceptibility; or medically significant hemorrhage within prior 30 days.
  • Any requirement for anti-coagulation, except for low molecular weight heparin.
  • 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.
  • 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.
  • Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the Investigator’s opinion, would increase the risk associated with study participation or study drug administration, or interfere with the interpretation of safety results.
  • Known history of hyperesthesia, hypoesthesia, paresthesia, dysesthesia, peripheral motor neuropathy, peripheral sensory, neuropathy, and polyneuropathy.
  • Major surgery (e.g., nephrectomy) less than 35 days prior to the first dose of study drug.
  • Focal radiation therapy less than 14 days prior to the first dose of study drug.
  • Receiving concomitant CYP3A4 inducers or strong CYP3A4 inhibitors
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of cabozantinib (e.g., malabsorptive disorder, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or small bowel resection).
  • Any of the following laboratory test findings: 1. WBC <2,000/mm3 2. Hemoglobin ≤9.0 g/dL 3. Neutrophils <1,500/mm3 4. Platelets <100,000/mm3 5. AST or ALT >3 x ULN (>5 x ULN if liver metastases are present) 6. Lipase and amylase > 1.5 ULN 7. Total Bilirubin >1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL) 8. Serum creatinine >1.5 x ULN or creatinine clearance <40 mL/min (measured or calculated by Cockroft-Gault formula) 9. Proteinuria: patients with ≥2+ protein on urine dipstick at baseline must undergo a 24-hour urine collection for protein then if > 1.0 g of protein patient will not be included.

Contact:

  • Reza ELAIDI, PhD
  • 00 33 1 56 09 23 40

Locations:

  • Hôpital Saint André, CHU de Bordeaux
  • Bordeaux 33075 France
  • Centre Francois Baclesse
  • Caen 14000 France
  • CHU Henri-Mondor
  • Creteil 94000 France
  • CHD Vendée
  • La Roche-sur-Yon 85925 France
  • Centre OSCAR LAMBRET LILLE
  • Lille 59000 France
  • Hôpital Européen Marseille
  • Marseille 13003 France
  • Institut Paoli Calmettes (IPC)
  • Marseille 13009 France
  • Centre Antoine Lacassagne
  • Nice 06100 France
  • Institut de Cancérologie du Gard – CHU Caremeau
  • Nîmes 30029 France
  • Hôpital Pitié-Salpêtrière
  • Paris 75013 France
  • Institut Mutualiste Montsouris
  • Paris 75014 France
  • Hôpital Européen Georges Pompidou
  • Paris 75015 France
  • Hôpital de la Croix Saint-Simon
  • Paris 75020 France
  • Hôpital Cochin
  • Paris 75679 France
  • Centre Hospitalier Lyon Sud – Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL)
  • Pierre Bénite 69310 France
  • Centre Eugene Marquis
  • Rennes 35042 France
  • Centre René Gauducheau ICO institut de Cancerologie de l’Ouest
  • Saint-Herblain 44805 France
  • Hôpitaux universitaires de Strasbourg
  • Strasbourg 67000 France
  • Hopital Foch
  • Suresnes 92151 France
  • Institut Claudius Regaud
  • Toulouse 31059 France
  • CHU Bretonneau
  • Tours 37000 France
  • Institut Gustave Roussy
  • Villejuif 94805 France

View trial on ClinicalTrials.gov

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