Clinical Trials /

Study of Optimized Management of Nivolumab Based on Response in Patients With Advanced RCC (OMNIVORE Study)

NCT03203473

Description:

This research study is studying two drugs at different time points as a possible treatment for advanced renal cell cancer The drugs involved in this study are: Nivolumab Ipilimumab

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Optimized Management of Nivolumab Based on Response in Patients With Advanced RCC (OMNIVORE Study)
  • Official Title: Phase II Study of Optimized Management of NIVOlumab Based on REsponse in Patients With Advanced Renal Cell Carcinoma (OMNIVORE Study)

Clinical Trial IDs

  • ORG STUDY ID: 17-064
  • NCT ID: NCT03203473

Conditions

  • Renal Cancer

Interventions

DrugSynonymsArms
IpilimumabYervoyArm A: Persistent (PR/CR)
NivolumabOpdivoArm A: Persistent (PR/CR)

Purpose

This research study is studying two drugs at different time points as a possible treatment for advanced renal cell cancer The drugs involved in this study are: Nivolumab Ipilimumab

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of investigational drugs to learn whether the drugs work in treating a
      specific disease. "Investigational" means that the intervention is being studied.

      Nivolumab and ipilimumab are antibodies (a type of human protein) that work to stimulate your
      body's immune system to fight tumor cells. The FDA (the U.S. Food and Drug Administration)
      has approved nivolumab as a treatment option for this disease; however, the FDA has not
      approved the way nivolumab and ipilimumab are being administered in this study. Ipilimumab is
      FDA approved for the treatment of melanoma (skin cancer) and has been previously studied in
      renal cell cancer.

      This study is being done to evaluate nivolumab treatment strategies based on each patients
      individual response to treatment. In participants who have a response to treatment, nivolumab
      will be stopped and participants will be closely monitored. In participants who do not have a
      response to treatment,the investigators will investigate whether the addition of ipilimumab
      improves a participant response to treatment. Participant blood and tissue samples will be
      collected to learn about how certain biomarkers and genes relate to participant outcomes.
    

Trial Arms

NameTypeDescriptionInterventions
Initial Primary TreatmentExperimentalTherapy with nivolumab IV every 2 weeks Serial imaging assessments every 8 weeks After confirmatory scans, patients are assigned to Arm A or Arm B.
  • Nivolumab
Arm A: Persistent (PR/CR)ExperimentalSerial imaging assessments every 8 weeks Therapy with nivolumab IV every 2 weeks If scans persistently show PR/CR, nivolumab is discontinued until progression. Nivolumab is re-initiated, and if there is subsequent progression, ipilimumab is added for x2 doses. Ipilimumab IV every 3 weeks (only in patients who progress after nivolumab re-initiation) If progression after nivolumab + ipilimumab, therapy discontinued. If SD/PR/CR, nivolumab is continued until progression.
  • Ipilimumab
  • Nivolumab
Arm B: Persistent (PD/SD)ExperimentalTherapy with nivolumab IV every 2 weeks Ipilimumab IV every 3 weeks Serial imaging assessments every 8 week If scans show SD/PR/CR, nivolumab continued until progression. If progression, therapy discontinued.
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        -  Age ≥ 18 years at the time of consent.

          -  ECOG Performance Status of ≤ 2 within 28 days prior to registration.

          -  Unresectable advanced or metastatic RCC to include both clear cell and non-clear
             histologies.

        oPatients who have suspected metastatic RCC, which has not yet been pathologically proven,
        may be enrolled if they plan to undergo a cytoreductive nephrectomy, metastectomy, or
        biopsy. Fresh tissue from one of these procedures can be used for the clinical trial
        requirements (eligibility #4) as well as serve as pathologic confirmation of RCC. The
        pathologic confirmation must be documented prior to C1D1.

          -  Availability at the study site of formalin-fixed, paraffin-embedded (FFPE) archival
             tumor specimens, when available, and willingness of the subject to undergo mandatory
             fresh tumor biopsy prior to treatment initiation unless determined medically unsafe or
             not feasible. If a target lesion is biopsied at screening, this lesion must be
             followed as non-target lesion after the biopsy unless it is the patient's only target
             lesion. If there is only one target lesion, it should be followed as a target lesion
             regardless.

               -  The archival specimen must contain adequate viable tumor tissue.

               -  The specimen may consist of a tissue block (preferred and should contain the
                  highest grade of tumor) or at least 30 unstained serial sections. Fine-needle
                  aspiration, brushings, cell pellet from pleural effusion, bone marrow
                  aspirate/biopsy are not acceptable.

          -  Previously untreated or treated subjects with no limit on prior lines of systemic
             therapies are allowed. Patient may have received prior adjuvant therapy.

          -  Measurable disease as defined by Response Evaluation Criteria In Solid Tumors RECIST
             1.1 within 28 days prior to registration.

               -  Demonstrate adequate organ function as defined in the table below. All screening
                  labs to be obtained within 28 days prior to first study treatment.

        System Laboratory Value

          -  Hematological

               -  White blood cell (WBC) ≥ 2500 cells/µL

               -  Absolute Neutrophil Count (ANC) ≥ 1500 cells/µL

               -  Platelet count (plt) ≥ 100,000/ µL

               -  Hemoglobin (Hgb) ≥ 9 g/dL (transfusions allowed)

               -  Absolute lymphocyte count ≥ 500 cells/µL

          -  Renal

             --Serum creatinine OR Calculated creatinine clearance ≤ 1.5 x ULN ≥ 40 mL/min

          -  Cockcroft-Gault formula will be used to calculate creatinine clearance

          -  Hepatic and Other

               -  Bilirubin ≤ 1.5 × upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) ≤ 2.5 × ULN

               -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN

               -  Alkaline Phosphatase ≤ 2.5 × ULN

          -  Subjects with documented liver metastases should have AST and ALT ≤ 5 x ULN. Subjects
             with documented liver or bone metastases should have alkaline phosphatase ≤ 5 x ULN

          -  Subjects with known Gilbert's disease should have a serum bilirubin ≤ 3 x ULN.

             --Albumin > 2.5 g/dL

          -  Coagulation

               -  International Normalized Ratio (INR) or Prothrombin Time (PT)

               -  Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN (unless on prophylactic
                  or therapeutic dosing with low molecular weight heparin)

                    -  Females of childbearing potential must have a negative serum pregnancy test
                       within 28 days prior to registration. NOTE: Females are considered of child
                       bearing potential unless they are surgically sterile (have undergone a
                       hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they
                       are naturally postmenopausal for at least 12 consecutive months.

                    -  Females of childbearing potential and males must be willing to abstain from
                       heterosexual activity or to use 2 forms of effective methods of
                       contraception from the time of informed consent until 120 days after
                       treatment discontinuation. The two contraception methods can be comprised of
                       two barrier methods, or a barrier method plus a hormonal method.

                    -  As determined by the enrolling physician or protocol designee, ability of
                       the subject to understand and comply with study procedures for the entire
                       length of the study.

        Exclusion Criteria

          -  Subjects meeting any of the criteria below may not participate in the study:

          -  Prior use of systemic checkpoint inhibitors for the management of metastatic RCC is
             excluded. Prior IFN-α or IL-2 is allowed.

          -  Receipt of any type of small molecule kinase inhibitor (including investigational
             kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy
             (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4
             weeks of enrollment.

          -  Treatment with systemic immunosuppressive medications including but not limited to:

          -  prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti-
             tumor necrosis factor (TNF) agents within 2 weeks of first study dose.

          -  Subjects who have received acute, low-dose systemic immunosuppressant medications may
             be enrolled (such as steroids for acute nausea or cancer-related pain ≤ 10 mg
             prednisone) may be enrolled sooner than 2 weeks of first study dose.

          -  Subjects with adrenal insufficiency on physiologic replacement doses of steroids may
             be enrolled (≤ 10 mg prednisone).

          -  The use of inhaled, topical, ocular or intra-articular corticosteroids and
             mineralocorticoids are allowed.

          -  Treatment with a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor
             (e.g. denosumab) within 2 weeks of first study dose.

          -  Radiotherapy for RCC within 14 days of first study treatment with the exception of a
             single fraction of radiation administered for palliation of symptoms.

          -  Known active metastases to the brain, spinal cord or leptomeninges unless adequately
             treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks of
             first study treatment as documented by magnetic resonance imaging (MRI) or
             computerized tomography (CT) imaging and having no ongoing requirement for steroids.

          -  Malignancies other than RCC within 5 years of first study treatment with the exception
             of those with negligible risk of metastases or death and/or treated with expected
             curative outcome (carcinoma in situ of the cervix, basal or squamous cell skin cancer,
             localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive
             urothelial carcinoma).

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion protein.

          -  Known hypersensitivity to any component of the nivolumab or ipilimumab product.

          -  Any active or recent history (within 6 months of first study dose) of autoimmune
             disease or syndrome that requires systemic corticosteroids (>10 mg daily prednisone
             equivalent) or immunosuppressive medications including but not limited to: myasthenia
             gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
             arthritis, inflammatory bowel disease, vascular thrombosis associated with
             anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome,
             Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
             Subjects with vitiligo, controlled type I diabetes mellitus, hypo- or hyperthyroid
             disease, or surgical adrenal insufficiency requiring hormone replacement therapy are
             permitted to enroll.

          -  Any condition requiring treatment with corticosteroids (>10 mg daily prednisone
             equivalent) or other immunosuppressive medication within 14 days of the first dose of
             study drug. Inhaled, topical, ocular or intra-articular steroids and adrenal
             replacement steroid doses ≤ 10 mg daily prednisone equivalents are permitted in the
             absence of active autoimmune disease.

          -  Uncontrolled adrenal insufficiency.

          -  History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             imaging CT of the chest. History of radiation pneumonitis in the radiation field is
             permitted.

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome.

          -  Known active or chronic hepatitis B infection (defined as having a positive hepatitis
             B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis
             B infection (defined as having a negative HBsAg test and positive antibody to
             hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in
             subjects with positive hepatitis B core antibody prior to first treatment start.

          -  Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible
             if PCR is negative for hepatitis C viral DNA.

          -  Severe infections within 4 weeks of first study treatment including but not limited to
             hospitalization for complications of infection, bacteremia, or severe pneumonia.

          -  Receipt of therapeutic oral or IV antibiotics within 2 weeks of first study treatment.
             Subjects receiving routine antibiotic prophylaxis (for dental extractions/procedures)
             are eligible.

          -  Significant cardiovascular disease such as New York Heart Association (NYHA) class III
             or greater, myocardial infarction within the previous 3 months, unstable arrhythmias,
             unstable angina. Patients with known coronary artery disease, congestive heart failure
             not meeting the above criteria, or left ventricular ejection fraction < 45% must be on
             a stable regimen that is optimized in the opinion of the treating physician, in
             consultation with a cardiologist when appropriate.

          -  Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on
             screening EKG > 500 msec.

          -  History of abdominal or tracheoesophageal fistula or GI perforation within 6 months of
             first study treatment.

          -  Clinical signs or symptoms of GI obstruction or requirement of routine parenteral
             nutrition.

          -  Evidence of abdominal free air not explained by paracentesis or recent surgical
             procedure.

          -  Serious, non-healing or dehiscing wound or active ulcer

          -  Major surgical procedure within 4 weeks of first study treatment.

          -  Presence of any toxicities attributed to prior anti-cancer therapy that are not
             resolved to grade 1 (National Cancer Institute Common Terminology Criteria for Adverse
             Events version 4.0) or baseline before administration of study drug.

          -  Prior allogenic stem cell or solid organ transplant.

          -  Administration of a live, attenuated vaccine within 4 weeks for first study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with persistent Partial Response (PR) or Complete Response (CR) at 1 year since nivolumab discontinuation (Arm A)
Time Frame:1 year after discontinuation with nivolumab
Safety Issue:
Description:Persistent PR or CR is defined as radiologic disease assessment performed every 8 weeks since primary nivolumab therapy. These radiologic disease assessments are evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. At 1 year after nivolumab discontinuation, the proportion of patients with persistent PR and CR will be evaluated by established methods (for Arm A only).

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:Disease will be evaluated every 8 or 12 weeks (depending on treatment) from study entry until disease progression, up to 24 months.
Safety Issue:
Description:The progression-free survival (PFS) rates for Arms A and B will each be summarized using the product-limit method of Kaplan-Meier. PFS is defined as the time from nivolumab discontinuation (Arm A) or from ipilimumab initiation (Arm B) until documented progression by RECIST version 1.1 criteria or death from any cause, censored at date last known progression-free for those who are alive and have not progressed.
Measure:Overall Survival
Time Frame:Patients will be followed from study entry to death or date last known alive, assessed up to 36 months.
Safety Issue:
Description:The overall survival (OS) rates for Arms A and B will each be summarized using the product-limit method of Kaplan-Meier. OS is defined as the time from nivolumab discontinuation (Arm A) or from ipilimumab initiation (Arm B) until death from any cause, censored at date last known alive or at the time of last assessment of follow-up.
Measure:Salvage therapy-free interval
Time Frame:On Arm A, the time from nivolumab discontinuation to the receipt of re-starting nivolumab, on average about 12 months.
Safety Issue:
Description:The salvage therapy rate is defined as time from nivolumab discontinuation (arm A) to the receipt of re-starting nivolumab.
Measure:Immune related objective response rate (irORR)
Time Frame:Disease will be evaluated every 8 or 12 weeks (depending on treatment) from study entry until disease progression per irORR criteria, up to 24 months.
Safety Issue:
Description:The irORR) in subjects in Arms A and B is defined according to immune-related Response Criteria (irRC) and will be estimated using exact binomial methods.
Measure:Safety and tolerability according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Time Frame:Throughout the course of the study, approximately 24 months after study entry
Safety Issue:
Description:In both Arms A and B, all adverse events recorded during the trial will be summarized for the safety population.The incidence of events that are new or worsening from the time of first dose of treatment will be summarized according to system organ class and/or preferred term, severity (based on CTCAE version 4), type of adverse event, and relation to study treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Renal Cancer

Last Updated