Axitinib Given on an Individualized Schedule for Metastatic Renal Cell Cancer
Condition: Metastatic Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell
Intervention: Axitinib
Intervention description: The intent is to maximize sustained dose intensity of axitinib based on individual tolerability using dose modification criteria
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney; Cancer; Axitinib; Pd-1 inhibitor; Pd-L1 inhibitor

Summary:

      Axitinib is a drug which is approved by the FDA for patients with advanced kidney cancer who
      have already received some treatment. It works by reducing blood flow to a tumor. Axitinib is
      normally give at 5mg twice per day and sometimes this dose is increased if patients tolerate
      it. The purpose of this study is to figure out a different way to decide which dose of
      axitinib each patient should receive based on the side effects they experience.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed, locally recurrent or metastatic clear cell renal cell
             carcinoma

          -  Has received one prior systemic therapy regimen for Metastatic Renal Cell Carcinoma
             (mRCC) directed against PD-1 and/or PD-L1 which must have been the most recent regimen

               -  Prior high-dose interleukin-2 therapy is permitted in addition to anti-PD(L)1
                  therapy, but is not required

               -  Prior bevacizumab or Vascular Endothelial Growth Factor (VEGF) Tyrosine Kinas
                  Inhibitor (TKI) is permitted either in combination with anti-PD(L)1 therapy OR as
                  monotherapy when given PRIOR to anti-PD(L)1 therapy

               -  Prior treatment with combined ipilimumab and nivolumab is permitted

               -  Prior axitinib in any setting is not permitted

               -  A minimum of two weeks since last dose of most recent renal cell cancer therapy
                  assuming resolution of clinically significant treatment-related toxicities to
                  grade 1, baseline, or controlled with supportive medications

          -  Evidence of measurable disease per RECIST 1.1.

          -  Karnofsky performance status ≥ 70 %.

          -  Adequate organ function as defined by:

               -  Absolute neutrophil count (ANC) ≥1,000/μL

               -  Platelets ≥100,000/μL

               -  Hemoglobin ≥9.0 g/dL

               -  Serum calcium ≤12.0 mg/dL

               -  Serum creatinine ≤2.0 x Upper Limit of Normal (ULN)

               -  Total serum bilirubin ≤1.5 x ULN

               -  SGOT≤2.5 x ULN and Serum Glutamic Pyruvic Transaminase (SGPT) ≤2.5x ULN

          -  Signed informed consent and willingness/ability to comply with scheduled visits,
             treatment plans, laboratory tests, and other study procedures

        Exclusion Criteria:

          -  Non clear cell Renal Cell Carcinoma (RCC)

          -  Major surgery within 4 weeks of starting the study treatment.

          -  Radiation therapy within 2 weeks of starting the study treatment. Prior palliative
             radiotherapy to metastatic lesion(s) is permitted, provided there is at least one
             measurable lesion that has not been irradiated.

          -  NCI CTCAE Version 4.03 grade 3 hemorrhage within 4 weeks of starting the study
             treatment.

          -  Any of the following within the 6 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident or transient
             ischemic attack.

          -  Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.03 grade ≥2. Controlled atrial
             fibrillation is permitted.

          -  Uncontrolled hypertension (>160/100 mm Hg despite optimal medical therapy)

          -  Concurrent treatment on another clinical trial. Supportive care trials or
             non-treatment trials, e.g. QOL, and imaging trials, are allowed.

          -  Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
             postmenopausal, or must agree to use effective contraception during the period of
             therapy. All female subjects with reproductive potential must have a negative
             pregnancy test (serum) prior to enrollment. Male subjects must be surgically sterile
             or must agree to use effective contraception during the period of therapy. The
             definition of effective contraception will be based on the judgment of the principal
             investigator or a designated associate

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the subject inappropriate for entry into
             this study.

          -  Uncontrolled Central Nervous System (CNS) metastases. Patients are considered to have
             controlled CNS metastases (and thus eligible) if they have completed local therapy
             (XRT and/or surgery) and are off steroids with clinical and radiographic stability 3
             months from the end of CNS-directed therapy.